maelstrom: Biological Overview | Evolutionary Homologs | Regulation | Developmental Biology | Effects of Mutation | References
Gene name - maelstrom

Synonyms -

Cytological map position - 80A1

Function - potential regulator of RNA processing or subcellular location

Keywords - spindle-class protein, A/P polarity, D/V polarity

Symbol - mael

FlyBase ID: FBgn0016034

Genetic map position - chr3L:22717333-22719334

Classification - HMG-box

Cellular location - nuclear and cytoplasmic

NCBI links: Precomputed BLAST | Entrez Gene | UniGene

Recent literature
Matsumoto, N., Sato, K., Nishimasu, H., Namba, Y., Miyakubi, K., Dohmae, N., Ishitani, R., Siomi, H., Siomi, M. C. and Nureki, O. (2015). Crystal structure and activity of the endoribonuclease domain of the piRNA pathway factor Maelstrom. Cell Rep 11: 366-375. PubMed ID: 25865890
PIWI-interacting RNAs (piRNAs) protect the genome from transposons in animal gonads. Maelstrom (Mael) is an evolutionarily conserved protein, composed of a high-mobility group (HMG) domain and a MAEL domain, and is essential for piRNA-mediated transcriptional transposon silencing in various species, such as Drosophila and mice. However, its structure and biochemical function have remained elusive. This study reports the crystal structure of the MAEL domain from Drosophila melanogaster Mael, at 1.6 A resolution. The structure reveals that the MAEL domain has an RNase H-like fold but lacks canonical catalytic residues conserved among RNase H-like superfamily nucleases. The biochemical analyses reveal that the MAEL domain exhibits single-stranded RNA (ssRNA)-specific endonuclease activity. Cell-based analyses further indicate that ssRNA cleavage activity appears dispensable for piRNA-mediated transcriptional transposon silencing in Drosophila. These findings provide clues toward understanding the multiple roles of Mael in the piRNA pathway.

A hallmark of germline cells across the animal kingdom is the presence of perinuclear, electron-dense granules called nuage. In many species examined, Vasa, a DEAD-box RNA helicase, is found in these morphologically distinct particles. Despite its evolutionary conservation, the function of nuage remains obscure. A null allele of maelstrom (mael) has been characterized. Maelstrom protein is localized to nuage in a Vasa-dependent manner. By phenotypic characterization, maelstrom has been defined as a spindle-class gene that affects Vasa modification. In a nuclear transport assay, it has been determined that Maelstrom shuttles between the nucleus and cytoplasm, which may indicate a nuclear origin for nuage components. Interestingly, Maelstrom, but not Vasa, depends on two genes involved in RNAi phenomena for its nuage localization: aubergine and spindle-E (spn-E). Furthermore, maelstrom mutant ovaries show mislocalization of two proteins involved in the microRNA and/or RNAi pathways, Dicer and Argonaute2 (see Argonaute I), suggesting a potential connection between nuage and the microRNA-pathway (Findley, 2003).

How germline status is established and maintained in sexually reproducing organisms is a fundamental question in developmental biology. A conserved feature of germ cells in species across the animal kingdom is the presence of a distinct morphological element called nuage. Ultrastructurally, nuage appears as electron-dense granules that are localized to the cytoplasmic face of the nuclear envelope. Despite the breadth of nuage in the animal kingdom, there is currently a lack of depth in understanding its function. In animals ranging from the nematode to vertebrates, the Vasa protein has been detected in these granules. Both nuage and Vasa thus offer potential clues as to what makes a germ cell unique (Findley, 2003).

One system with high potential for understanding the role of nuage is Drosophila. In females, Vasa-positive germline granules are continuously present throughout the life cycle, taking one of two forms, nuage or pole plasm. Pole plasm, which contains polar granules, is a determinant that is both necessary and sufficient to induce formation of the germ lineage in early embryogenesis. In Drosophila, nuage is first detectable when primordial germ cells are formed; it persists through adulthood, where it is present in all germ cell types of the ovary (Findley, 2003).

In Drosophila, three proteins are known to localize to nuage: Vasa, Aubergine and Tudor. The sequence or mutant phenotype of each gene suggests a role in post-transcriptional RNA function. Vasa is a DEAD-box RNA helicase required for nurse cell-to-oocyte transport of several mRNAs critical to oocyte patterning. Vasa is also required for efficient translation of several key proteins in oogenesis, and itself interacts both physically and genetically with a Drosophila homolog of yeast, Translation Initiation Factor 2 (dIF2). Vasa is thus potentially implicated in translational control. Aubergine is a member of the RDE1 (for RNAi defective)/AGO1 (Argonaute1) protein family, homologs of which are required in both RNAi and developmental processes in diverse organisms. Aubergine is required, during oogenesis, for efficient translation of Oskar, which is pivotal in initiating pole plasm assembly. Aubergine is also required for RNAi in late oogenesis. Tudor, a novel protein, comprises ten copies of an ~120 residue motif (the 'Tudor Domain', pfam00567) present in several proteins involved or implicated in RNA-binding capacities. The domain has been suggested to mediate protein-protein interactions. Drosophila Tudor is required to mediate transfer of mitochondrial ribosomal RNAs from mitochondria to the surface of polar granules during pole cell formation in early embryogenesis (Amikura, 2001). A role for Tudor prior to pole plasm assembly, however, has not been described (Findley, 2003 and references therein).

Aubergine and vasa are members of a larger group of female sterile mutants, the spindle (spn) class, which produces eggshells with variable anteroposterior (AP) and dorsoventral (DV) axis defects. In most of the characterized spn mutants, the etiology of these patterning defects has be traced to a failure in Gurken (a TGFalpha homolog) presentation in developing egg chambers. Each spn mutant also has a meiotic progression defect: by stage 4 in a normal egg chamber, the DNA within the oocyte nucleus (germinal vesicle) condenses into a compact sphere called a karyosome after successful meiotic recombination. Mutants in all spn genes fail to form a karyosome. The characterized spn genes fall into two groups: those whose gene products are directly required for recombinational DNA repair steps within the germinal vesicle [e.g. okra (okr), spn-B and spn-C] and those whose protein sequence or localization suggest indirect involvement in meiotic progression [e.g. aubergine, vasa and spn-E]. The spn mutants, as a group, demonstrate that meiotic and patterning processes intersect during oogenesis (Findley, 2003).

A null allele of the maelstrom gene, which encodes a novel protein with a human homolog, has been identified and characterized. The mutant displays each of the defects in oocyte development common to the spindle-class. Maelstrom localizes to nuage in a Vasa-dependent manner and maelstrom is required for proper modification of Vasa. Through mutant analysis, this study begins to unravel genetic dependencies of nuage particle assembly (Findley, 2003).

It is unknown whether the known nuage proteins act in a common pathway before their convergence in nuage particles. To begin to answer this question, attempts were made to determine genetic dependencies for nuage particle assembly. AubGFP is known to depend on vasa function for its nuage localization (Harris, 2001). Maelstrom and Vasa localization were analyzed in wild-type, maelstrom, vasa, aubergine and spn-E backgrounds. Maelstrom protein levels proved to be quite variable among ovarioles of single mutant backgrounds. So, in order to compare localization, individual ovarioles were examined in which Maelstrom levels were not significantly reduced. Virtually no Maelstrom immunoreactive signal is present in maelstrom mutants, whereas Vasa is largely maintained in nuage. By contrast, the perinuclear accumulation of Maelstrom is virtually absent in the vasa null mutant, suggesting that Maelstrom localization in nuage is Vasa dependent. Maelstrom's distribution was examined in several vasa point mutants, in the hope of correlating functional domains in the protein with nuage organizational function. Of particular interest were two vasa EMS alleles, vas011 and vas014, each of which produces a protein devoid of RNA binding and unwinding activities. In both of these mutants, Vasa and Maelstrom colocalization in nuage is largely maintained. Vasa and Maelstrom localization were analyzed in several allelic combinations of aubergine, since a null for this gene has not been described. Both aubHN2 and aubN11 alleles encode truncated proteins. In this and other aubergine mutant combinations, the normal concentration of Maelstrom in nuage is severely depleted in all germline cells. Vasa is largely maintained in perinuclear localization in this mutant background, but the normally discrete particles are less obvious; instead, Vasa appears as a more uniform perinuclear band (Findley, 2003).

Spn-E encodes a putative Dex/hD-box RNA helicase, required for proper localization of several oocyte-destined RNAs and proteins over the course of oogenesis. While the localization of Spindle-E in the ovary has not been determined, its involvement in both RNAi and oogenesis, like Aubergine, prompted its inclusion in this analysis. As with aubergine mutants, the concentration of Maelstrom in perinuclear particles is lost in strong spn-E allelic combinations, spn-E616/hlsDelta125 and spn-Ehls3987/hlsDelta125. Vasa retains a perinuclear concentration in spn-E ovaries, but as in aubergine, the normal particulate appearance of nuage is less pronounced. Localization analysis has been extended to include the remaining members of the better characterized spn-class mutants, spn-A, spn-B, spn-C, spn-D and okr. Of particular interest was spn-B, which has been shown to modify Vasa as a consequence of meiotic checkpoint activation. The dependency of Maelstrom on Vasa for its localization could, in principle, be affected if Vasa is aberrant. However, in multiple allelic combinations of well-characterized spn genes (spn-B, spn-D and okr) and uncloned spn genes (spn-A and spn-C), colocalization of Vasa and Maelstrom in nuage particles was unperturbed at all stages of oogenesis (Findley, 2003).

Normally, a variety of RNAs required for proper oocyte function are transcribed, exported from nurse cell nuclei and transported to the oocyte. Since this process is defective in vasa ovaries, transport in maelstrom ovarioles was assessed, with the aim of resolving potential functions of individual nuage components. It was found that transport of several of these mRNAs, including oskar, orb and BicD, is unaltered in maelstrom ovaries (Findley, 2003).

The dissociation of Maelstrom from nuage particles in aubergine and spn-E backgrounds was intriguing in light of their requirement in RNAi in Drosophila spermatogenesis and late oogenesis. Importantly, proteins (or homologs) of RNAi pathway components also act in micro RNA (miRNA) processing. Since miRNAs have been shown to regulate RNA translation, it is conceivable that miRNAs are assembled in RNP particles formed in nuage. In this setting, nuage could represent a step in the generation of specificity in translational control in the germline. To explore this potential relationship between nuage and RNAi/miRNA processing pathways, the localization of additional RNAi components was examined in wild-type and maelstrom ovaries. Argonaute1 and Argonaute2 are RDE1/AGO1 homologs required for RNAi in Drosophila. Dicer is the core RNase of RNAi in Drosophila; it is also required for production of the small RNA effectors of the RNAi and miRNA pathways in C. elegans. In vertebrate cell lines, Dicer is primarily cytoplasmic. In wild-type Drosophila ovarioles, Dicer and AGO1 appear uniform and cytoplasmic in nurse cell cytoplasm; AGO2 appears cytoplasmic but relatively more granular. In maelstrom ovaries, AGO1 distribution is relatively unperturbed. However, AGO2 and Dicer are both dramatically mislocalized in maelstrom ovarioles. Beginning around stage 3, Dicer aggregates in discrete, often perinuclear foci in nurse cells. AGO2 is observed in perinuclear regions of nurse cells, which, by contrast, can colocalize with Vasa in nuage (Findley, 2003).

The failure of maelstrom oocytes to proceed to the karyosome stage, to establish cytoplasmic polarity and to accumulate Gurken qualifies the inclusion of maelstrom in the spindle class. Maelstrom is a component of Drosophila nuage and is required for proper modification (or processing) of a key nuage component, Vasa. Maelstrom is also present within the nucleus and cytoplasm of all germline cells, and can shuttle between these compartments in a CRM1-dependent manner. Of the known nuage-localizing proteins, Vasa appears to be a pivotal organizer or nucleator of nuage, whereas Maelstrom can be dissociated from nuage particles in aubergine and spn-E mutants. Furthermore, Dicer and AGO2 are mislocalized in the maelstrom background (Findley, 2003).

The characterized spn genes currently fall into two general classes: those that encode proteins that are likely to be directly involved in meiotic recombinational repair, such as okr, spn-B and spn-C; and those, such as maelstrom and vasa, whose mutant meiotic phenotype, protein sequence and/or localization suggest indirect roles. Work presented in this study suggests that the spn mutants can be sorted by an additional criterion: those that are also required for nuage assembly (vasa, aubergine, maelstrom and spn-E) and those that are not (spn-A, spn-B, spn-C, spn-D and okra). Taken together, these data suggest that the Vasa-like group of spn genes are essential in general 'nuage activities' in all cells of the germline. The activity of the spn-B-class genes, which are involved in recombination or meiotic checkpoint, could represent one avenue through which to use or modulate existing nuage functions that are operative within the germline cyst as a whole. Such nuage-related processes, if inactivated or defective, might culminate in polarity and translational defects within the oocyte (Findley, 2003).

Within the time frame of the life cycle of the female fly, pole plasm, in its mature form, is ephemeral. Nuage, by contrast, is present in morphologically stable form from mid-embryogenesis through to late oogenesis in the adult. Nuage is thus a feature that is specific to established germ cells, perhaps reinstated by pole plasm components in early embryogenesis. Maelstrom is unique among previously identified Drosophila nuage components, which are also concentrated in pole plasm. Maelstrom is thus the first identified nuage-specific component in Drosophila. Nuage is the most conserved form of the Vasa-positive germline granule: it is present in germ cells of diverse organisms, including mammals, which do not use a pole plasm equivalent. The cell biology of nuage, however, remains largely unexplored. Since nuage components are also present in the nucleus and cytoplasm, these particles may represent a morphologically distinct form (or kinetic intermediate) of a nucleocytoplasmic continuum. Maelstrom can shuttle between nuclear and cytoplasmic compartments. The observation that Vasa shows only a slight redistribution to the nuclear compartment implies that these proteins are not necessarily always associated. This begs the question of whether components of nuage converge on and diverge from perinuclear particles from separate pathways or subcellular compartments. As more nuclear transport tools become available, how these particles are formed will be better resolved (Findley, 2003).

Within egg chambers, a number of mRNAs crucial for oocyte patterning are synthesized in nurse cells and transported to the developing oocyte. The oocyte represents a discrete compartment in the continuous cytoplasm of the germline cyst, and precise spatiotemporal control of nurse cell-derived mRNA translation is crucial for proper development. Between transcription in nurse cell nuclei and their ultimate translation, oocyte-destined RNAs are likely to be associated with factors required to mediate both localization and translational control. Heterogeneous nuclear ribonucleoproteins (hnRNP-proteins) associated with mRNAs during their transit from nucleus to cytoplasm can play key roles in mRNA localization and translational control. Similarly, splicing factors have been shown to continue their association with mRNA into cytoplasm. And although the exchange of nuclear for cytoplasmic RNA-binding proteins has been demonstrated, the location and regulation of such exchange processes are poorly understood. A working hypothesis is that nuage in the Drosophila germline (and other systems) functions in such an exchange process. In this capacity, nuage might be a platform for, or represent a kinetic intermediate of, cytoplasmic ribonucleoprotein (RNP) particle assembly. The perinuclear localization of nuage and the observation that Maelstrom shuttles between compartments are consistent with this role. Two additional lines of evidence support the proposition. The first is that nuage ultrastructurally interfaces with sponge bodies, which are highly abundant, RNA-rich particles present in the cytoplasm of nurse cells and the oocyte. Mounting evidence points to a role for the sponge body as a vehicle for transport of RNP complexes between nurse cells and the oocyte. Sponge bodies are also highly enriched for several regulatory proteins, including Exuperantia, DEAD-box RNA helicase Me31B and cold shock protein YPS, that can be purified as an RNase-sensitive RNP complex. This complex, by purification or localization, is associated with numerous oocyte-destined RNAs, such as oskar and bicoid. Ultrastructurally, the perinuclear fraction of sponge body particles appear to embed individual nuage particles, a morphological association that implicates the interface as one possible segment in what may be a continuous RNP assembly process(Findley, 2003 and references therein).

The second line of evidence is that three of the proteins present in, or required for, nuage particle assembly (Aubergine, Vasa and Spn-E) are also implicated in post-transcriptional RNA-related capacities. Aubergine mutants fail to translate Oskar efficiently, despite proper localization of oskar mRNA to the oocyte posterior. Aubergine is concentrated in two distinct regions within germline cysts: in nuage and also in pole plasm. Thus, aubergine function may be required for proper Oskar translation before oskar mRNA is even transported to the oocyte posterior. Vasa is a DEAD-box RNA helicase, a class of proteins thought to act as RNA chaperones (Findley, 2003 and references therein).

Vasa-null egg chambers display a systemic failure in mRNA targeting. This could be attributable, in part, to the loss of interface of nuage with sponge bodies; vasa null ovaries are devoid of nuage at the ultrastructural level. spn-E encodes a Dex/hD class (putative) RNA helicase. spn-E ovaries contain enlarged sponge bodies and display defects in the localization of several normally oocyte-destined molecules, including bicoid RNA, as well as BicD(GFP) and Dynein Heavy Chain. Each of these molecules is largely retained in mutant nurse cells, accumulating in the vicinity of ring canals. The specificity of the localization defect suggests an underlying defect in transport through ring canals, which is a discrete, microtubule-independent step in nurse cell-to-oocyte transport. This defect (together with the nuage assembly defect of spn-E) is consistent with the hypothesis that nuage may function in formation of RNPs required for correct mRNA localization in the Drosophila germline (Findley, 2003).

A tantalizing possibility for nuage is that it may function at some point in miRNA and/or RNP particle assembly processes. This hypothesis is supported by the mislocalization of Dicer and AGO2 to perinuclear regions of germline cells in the maelstrom mutant. Such discrete redistributions of proteins could reflect an accretion of intermediate in a normally maelstrom-mediated step. A connection is further insinuated by the requirement of both aubergine and spn-E in the assembly of nuage particles. In mutants of both genes, Maelstrom is dissociated from perinuclear Vasa particles in all germline cells. The dissociation is interesting because both aubergine and spn-E have a common requirement in double-stranded RNA-mediated gene silencing in both Drosophila spermatogenesis and late oogenesis. In the testis, spn-E is required for silencing of retrotransposons (e.g. copia) and both spn-E and aubergine are required for silencing of genomic tandem repeats (e.g. Stellate). Mutants in either gene relieve RNAi-mediated suppression of respective target genes. The fact that each is also required for proper mRNA localization or translation raises the possibility that these proteins could function as common components in the allied miRNA pathway. RNAi and miRNA are mechanistically related: each pathway processes a dsRNA substrate, using a common processing factor, Dicer, to generate the respective small RNA effectors of each pathway. In C. elegans, 24 RDE1/AGO1 homologs have been identified. The studied homologs are required in either RNAi or miRNA processing, but in not both pathways. The Drosophila genome encodes only five RDE1/AGO1 homologs: Piwi, Aubergine, AGO1, AGO2 and AGO3, which may necessitate dual usage in both miRNA and RNAi pathways (Findley, 2003).

Recent reports suggest that hundreds of miRNAs exist in metazoans. These miRNAs are thought to be modulators of target mRNA translation, although additional functions have been hypothesized. Indeed, miRNAs might represent a common means of post-transcriptional regulation of gene expression in both vertebrates and invertebrates. It is known for many cell types, including neurons and oocytes, that translation and localization of mRNA is controlled by RNA-binding proteins. However, the specificity of this process is poorly understood. In some cases, a sequence-specific RNA binding protein is found to be involved; in other cases a combinatorial action of many hnRNPs is proposed. The abundance of miRNAs raises the possibility that these small RNAs could generate the missing specificity: miRNAs bound to target mRNAs are predicted to form a loop structure that could be recognized by multiple RNA-binding proteins, allowing for assembly of a full RNP particle. In the context of oogenesis, miRNAs could provide an added level of control by conferring specificity through nucleation or regulated assembly of translational (and possibly localization) control factors on RNAs. The data presented in this study suggest that nuage function may be involved in the miRNA or RNAi pathways. Future experiments should be aimed at determining the role of nuage components in miRNA precursor maturation or in assembly of mature miRNAs with their target mRNAs (Findley, 2003).


cDNA clone length - 1572 bp

Bases in 5' UTR - 265

Exons - 5

Bases in 3' UTR - 117


Amino Acids - 459

Structural Domains

Homologs of Maelstrom can be identified in mosquito (Anopheles gambiae), honey bee (Apis mellifera), mouse and human. A ClustalW alignment of the Drosophila, mosquito and human homologs shows 7.3% identity and 25.9% similarity shared between the three proteins. Fourth iteration Psi-blast searches with the Drosophila homolog gives overall E-values of e-151 (to the mosquito homolog, agCP12344) and e-150 (to the human homolog, FLJ14904). In addition, a partial potential HMG-box is found in Drosophila Maelstrom (residues 2-50), whereas a canonical HMG-box is found in the human homolog (residues 5-65) (Findley, 2003).


Mouse maelstrom, a component of nuage, is essential for spermatogenesis and transposon repression in meiosis

Tight control of transposon activity is essential for the integrity of the germline. Recently, a germ-cell-specific organelle, nuage, was proposed to play a role in transposon repression. To test this hypothesis, a murine homolog of a Drosophila nuage protein Maelstrom was disrupted. Effects on male meiotic chromosome synapsis and derepression of transposable elements (TEs) were observed. In the adult Mael-/- testes, LINE-1 (L1) derepression occurred at the onset of meiosis. As a result, Mael-/- spermatocytes were flooded with L1 ribonucleoproteins (RNPs) that accumulated in large cytoplasmic enclaves and nuclei. Mael-/- spermatocytes with nuclear L1 RNPs exhibited massive DNA damage and severe chromosome asynapsis even in the absence of SPO11-generated meiotic double-strand breaks. This study demonstrates that MAEL, a nuage component, is indispensable for the silencing of TEs and identifies the initiation of meiosis as an important step in TE control in the male germline (Soper, 2008).

These studies of Mael mutant testes suggest a close functional relationship of MAEL with MIWI2 and MILI, two of three murine PIWI-like proteins. Mael-, Mili-, and Miwi2-deficient spermatocytes fail to complete meiotic prophase and to assemble functional synaptonemal complexes. Interestingly Mael- and Miwi2-deficient spermatocytes develop identical atypical morphologies (not reported for the Mili mutant) prior to their elimination by apoptosis. Furthermore, Mael and Miwi2 mutant testes exhibit a common pattern of TE activation (high levels of L1 expression and only modest derepression of IAP) that contrasts TE expression in the Mili mutant. These data suggest that MAEL plays a more prominent role in the MIWI2-dependent processes, possibly at a post-piRNA production step (since no reduction of prepachytene piRNAs was observed in the Mael mutant). Given that MAEL was reported to shuttle between the nucleus and cytoplasm in Drosophila and MAEL complexes were observed in the nucleus and at nuclear pores in this study, it is speculated that MAEL may facilitate trafficking of MIWI2-piRNA complexes to or from nuage (Soper, 2008).

Of particular interest is the observation of L1 expression at the onset of meiosis in the absence of MAEL. It is generally accepted that de novo DNA methylation of TEs in gonocytes of late gestation male fetuses is crucial for TE repression in the male germline. In addition, recent studies demonstrated essential roles of MILI and MIWI2 in de novo DNA methylation of TEs in fetal gonocytes. Once established in the fetal germ cells, repressive DNA methylation of TEs is expected to be maintained in the male germline into the adulthood. One would expect, therefore, L1 derepression to be apparent in both premeiotic and meiotic germ cell populations of an adult Mael-deficient testis. In this study, however, L1 RNA and MAEL isoform ORF1p are found exclusively in the adult Mael-/- meiotic germ cells and not in the spermatogonia. L1 ORF1p expression starts in preleptotene Mael-/- spermatocytes (characterized by the premeiotic S phase) and persists until germ cell elimination. These results suggest a more dynamic control of TE expression at the onset of meiosis and parallel the findings of an earlier study of L1 expression in the testes. Taken together, the two studies suggest a tantalizing possibility of the existence of an epigenetic reprogramming step at the onset of meiosis that involves transient derepression of TEs (Soper, 2008).

This study provides compelling evidence of a highly detrimental effect of TE derepression on the male germline. L1 transcriptional derepression in the absence of MAEL leads to flooding of spermatocytes with ORF1p found both in the cytoplasm and nuclei. Cytoplasmic ORF1p is often present in large enclaves that contain vast numbers of 25-30 nm particles that could be identical to L1 RNPs observed previously. Nuclear ORF1p localization strongly correlates with accumulation of severe DNA damage that is mechanistically distinct from developmentally programmed SPO11-generated meiotic DSBs. The presence of numerous RAD51 foci in the absence of SPO11 further supports the idea that Mael-/- spermatocytes harbor an endonuclease that is absent or inactive in wild-type and Spo11-/- spermatocytes. A leading candidate for such an enzyme is L1-encoded ORF2p, whose N terminus has endonuclease activity that is required for retrotransposition and generation of DSBs in cultured human cell lines. Finally, nuclear accumulation of L1 RNPs also strongly correlates with defects in chromosome synapsis. A great majority of Mael-/- spermatocytes exhibiting the most severe disruption of synapsis contain nuclear L1 RNPs (89% of cells in the univalent class). The precise mechanism of suppression of synapsis by L1 is yet to be understood, but the results already suggest a strong correlation between the frequency of nuclear L1 RNPs, the severity of DNA damage, and asynapsis. Cumulatively, this study vividly illustrates an absolute requirement for efficient TE restraining mechanisms in the mammalian germline (Soper, 2008).

maelstrom: Regulation | Developmental Biology | Effects of Mutation | References

date revised: 25 February 2009

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