Meiosis regulator and mRNA stability factor 1: Biological Overview | References |
| Meiosis regulator and mRNA stability factor 1 -
Cytological map position - 40F7-40F7
Function - RNA-binding protein
Keywords - post-transcriptional effector domain that recruits CCR4-NOT deadenylase complex to shorten target mRNA poly-A tails and suppress their translation - ensures proper oocyte maturation by regulating nanos expression - transition from meiosis I to II is compromised mutant oocytes
Symbol - Marf1
FlyBase ID: FBgn0039972
Genetic map position - chr2L:22,311,927-22,368,776
Cellular location - cytoplasmic
Post-transcriptional regulation of gene expression plays an essential role during oocyte
RNA-binding proteins (RBPs) mediate post-transcriptional gene regulation by determining molecular fates of target RNAs. In addition to RNA-binding domains, RBPs often have additional auxiliary domains. These auxiliary domains may function as effector domains for post-transcriptional gene regulation directly through enzymatic activity or indirectly by mediating protein-protein interaction. Identifying these effector domains and their molecular functions is critical to understand the roles of RBPs in post-transcriptional gene regulatory mechanism (Zhu, 2018).
MARF1 is an RBP consisting of one RNA-recognition motif (RRM) followed by several tandem LOTUS domains (Limkain, Oskar, and Tudor containing proteins 5 and 7. Also called OST-HTH). Previous studies showed that mouse MARF1 is required for completion of meiosis in oogenesis by reducing protein and mRNA levels of retrotransposons and a few endogenous genes (Su, 2012a; Su, 2012b). However, the molecular mechanism by which MARF1 regulates gene expression remains unclear (Zhu, 2018).
LOTUS domains are conserved in bacteria, fungi, plants, and animals. In animals, LOTUS domain proteins are expressed almost exclusively in the germline and are implicated in RNA regulation. In Drosophila, these LOTUS domain proteins include Oskar, Tejas (human TDRD5), Tapas (human TDRD7), and MARF1 (Meiosis Regulator And mRNA Stability Factor 1 = GC17018. Human MARF1). However, the molecular function of the conserved LOTUS domain is not fully understood (Zhu, 2018).
This work studied the biological and molecular functions of Drosophila MARF1 and its LOTUS domains. MARF1 is essential for proper oocyte maturation by regulating cyclin protein levels. When tethered to a reporter mRNA, MARF1 caused shortening of reporter mRNA poly-A tail and reduced reporter protein level. This activity was mediated by MARF1 LOTUS domain. Consistent with this finding, it was found that MARF1 binds the CCR4-NOT deadenylase complex via its LOTUS domain. Furthermore, it was found that MARF1 binds cyclin A mRNA, shortens its poly-A tail, and reduces Cyclin A protein level during oocyte maturation. Thus, this study uncovered the biological and molecular functions of Drosophila MARF1 and defined its conserved LOTUS domains as a post-transcriptional effector domain to recruit the CCR4-NOT deadenylase complex to shorten target mRNA poly-A tails and suppress translation of the mRNAs (Zhu, 2018).
MARF1 is expressed in late-stage oocytes and is required for proper oocyte maturation by regulating cyclin protein levels. MARF1 binds the CCR4-NOT deadenylase complex via its LOTUS domain to shorten target mRNA poly-A tails and thus reducing cyclin protein levels without changing cyclin mRNA levels. Thus, MARF1 LOTUS domain is defined as a post-transcriptional effector domain that binds the CCR4-NOT deadenylase complex (Zhu, 2018).
Recent studies by others showed that the LOTUS domains of Drosophila Oskar, Tejas, and Tapas bind germline DEAD-box RNA helicase Vasa to stimulate Vasa ATPase and helicase activities. Crystallographic studies showed that the LOTUS domain of Oskar forms a homodimer and that each of the monomer subunits binds the C-terminal domain of the Vasa DEAD-box helicase core on the side opposite to the dimerization interface. In contrast, this study shows that the MARF1 LOTUS domain binds the CCR4-NOT deadenylase complex, but does not bind Vasa, Oskar, or another molecule of MARF1 (Zhu, 2018).
The LOTUS domains found in Oskar, Tejas, and Tapas, but not MARF1, have a C-terminal extension, which is required for interaction with Vasa. Hence the LOTUS domains are divided into two subclasses: (1) extended LOTUS (eLOTUS) domain that is present in Oskar, Tejas, and Tapas, has a C-terminal extension, and binds Vasa, and (2) minimal LOTUS (mLOTUS) domain that is present in MARF1, lacks a C-terminal extension, does not bind Vasa, and instead binds the CCR4-NOT deadenylase complex. Thus, although eLOTUS and mLOTUS domains share core sequence homology except for the C-terminal extension, they mediate distinct protein-protein interactions. Interestingly, eLOTUS proteins (Oskar, Tejas/TDRD5, Tapas/TDRD7) contain a single eLOTUS domain while mLOTUS proteins (MARF1) contain multiple tandem mLOTUS domains (Zhu, 2018).
This study also showed that MARF1 binds cyclin A mRNA. In MARF1null mutant late-stage oocytes, cyclin A mRNA poly-A tail is longer and Cyclin A protein level is increased, without change in the cyclin A mRNA level. The degradation rate of Cyclin A protein was not changed in MARF1null oocytes compared with control oocytes in vitro. These results indicate that in control late-stage oocytes, MARF1 post-transcriptionally regulates Cyclin A protein level by binding cyclin A mRNA, shortening cyclin A mRNA poly-A tail, and reducing Cyclin A protein level. In contrast, poly-A shortening of cyclin A mRNA is lost in MARF1null oocytes, resulting in an accumulation of Cyclin A protein. Cyclin A is the only protein found that is increased in its level in MARF1 mutant oocytes (Zhu, 2018).
Based on these findings, a model is proposed for MARF1 molecular function. The MARF1 RRM binds specific target mRNAs, such as cyclin A mRNA, and the MARF1 mLOTUS domains recruit the CCR4-NOT deadenylase complex (see Models for MARF1 function in oocytes). This results in shortening of target mRNA poly-A tail and reduction of protein level produced from target mRNAs. The multiple, tandem mLOTUS domain may recruit multiple CCR4-NOT deadenylase complexes per single MARF1 molecule and single target mRNA, enabling efficient poly-A shortening (Zhu, 2018).
Using this model, it is proposed that MARF1 reduces Cyclin A protein level in stages 12-14 oocytes. This regulated reduction of Cyclin A protein level leads to expression of Cyclin B and Cyclin B3 proteins. This cyclin proteins expresson profile leads to stabilization of CDK1 protein and phosphorylation of CDK1 Tyr15 residue. Increase CDK1 and phosphorylation of CDK1 Tyr15 residue result in phosphorylation of appropriate target proteins of CDK1 in stage 14 oocytes. Proper global protein phosphorylation profile allows germplasm localization of Vasa and Aub and normal yolk distribution in stage 14 oocytes. As stage 14 oocytes traverse through the oviduct, meiotic Metaphase I arrest is released to complete meiosis and produce normal eggs (Zhu, 2018).
Consequently, it is speculated that Cyclin A is the main and/or most upstream target of MARF1. Persisted Cyclin A protein level in MARF1 mutant late-stage oocytes arrest them in an abnormal state rather than proceeding to a normal stage 14 including decreased protein levels of Cyclin B and Cyclin B3. Dysregulation of the three cyclin proteins levels results in the decreased CDK1 protein level and the decreased Tyr15 phosphorylation of CDK1. Dysregulation of cyclins and CDK1 alters global phosphorylation pattern. The altered phosphorylation pattern results in the loss of germplasm localization of Vasa and Aub. These together cause meiotic failure and complete sterility in MARF1 mutants (Zhu, 2018).
MARF1 seems to target specific mRNAs for gene silencing in diverse species. This study identified cyclin A mRNA as a target of Drosophila MARF1. Mouse MARF1 reduces protein and mRNA levels of retrotransposons and a few endogenous genes such as PPP2CB, suggesting that they are targets of the post-transcriptional silencing by mouse MARF1. Knockdown of human MARF1 causes upregulation of IFl44L mRNA, suggesting that IFl44L mRNA a target of human MARF1. Post-transcriptional gene silencing of target mRNAs in fly, mouse, and human MARF1 suggests that mLOTUS-domain directed recruitment of the CCR4-NOT deadenylase complex may be a widely conserved mechanism (Zhu, 2018).
LOTUS domains are found not only in animals but also in bacteria, fungi, and plants. LOTUS domains found in bacteria, fungi, and plants are more similar to the animal mLOTUS domains since they lack the C-terminal extension found in the animal eLOTUS domains. This suggests that the mLOTUS domain may be more ancient than the eLOTUS domain. It will be interesting to investigate the functions of these LOTUS domains found in non-animals, particularly the function of bacterial LOTUS domains, since bacteria do not have a poly-A tail in their mRNAs or CCR4-NOT deadenylase complex (Zhu, 2018).
Meiosis and oocyte maturation are tightly regulated processes. The meiosis arrest female 1 (MARF1) gene is essential for meiotic progression in animals; however, its detailed function remains unclear. This study examined the molecular mechanism of dMarf1, a Drosophila homolog of MARF1 encoding an OST and RNA Recognition Motif (RRM) -containing protein for meiotic progression and oocyte maturation. Although oogenesis progressed in females carrying a dMarf1 loss-of-function allele, the dMarf1 mutant oocytes were found to contain arrested meiotic spindles or disrupted microtubule structures, indicating that the transition from meiosis I to II was compromised in these oocytes. The expression of the full-length dMarf1 transgene, but none of the variants lacking the OST and RRM motifs or the 47 conserved C-terminal residues among insect groups, rescued the meiotic defect in dMarf1 mutant oocytes. These results indicate that these conserved residues are important for dMarf1 function. Immunoprecipitation of Myc-dMarf1 revealed that several mRNAs are bound to dMarf1. Of those, the protein expression of nanos (nos), but not its mRNA, was affected in the absence of dMarf1. In the control, the expression of Nos protein became downregulated during the late stages of oogenesis, while it remained high in dMarf1 mutant oocytes. It is proposed that dMarf1 translationally represses nos by binding to its mRNA. Furthermore, the downregulation of Nos induces cycB expression, which in turn activates the CycB/Cdk1 complex at the onset of oocyte maturation (Kawaguchi, 2020).
Nos is an evolutionary conserved protein that play important roles in early embryogenesis, formation of primordial germ cells and maintenance of germline stem cells (GSCs). However, the function of Nos during late oogenesis has not been described yet. Nos protein expression reaches the maximum around stage 10 of oogenesis and immediately reduces thereafter. This suggests that Nos expression is tightly regulated during late oogenesis. The current results indicate that dMarf1 regulates Nos expression by inhibiting its translation in late oogenesis. In the absence of dMarf1 expression during early-to-mid oogenesis, Nos might repress cycB to prevent the premature release of meiotic arrest until stage 10 of oogenesis. These results suggest that dMarf1 may coordinate oocyte maturation during late oogenesis in Drosophila; moreover, dMarf1 is dominantly expressed after stage 10, and binds to nos mRNA to repress its translation and reduce its expression. Consequently, Nos expression almost disappears at stages 12-14. Reduced expression of Nos induces the release of cycB mRNA from repression and promotes CycB translation. Subsequently, CycB binds to Cdk1 to form the active MPF complex to promote meiosis. Therefore, dMarf1 plays an important role in the release of the second meiotic arrest to drive embryogenesis (Kawaguchi, 2020).
The MARF1 gene is evolutionarily conserved in animals; most proteins of the MARF1 family contain three major domains: NYN, OST (also known as LOTUS), and RRM. Although the ribonuclease activity of NYN is essential for MARF1 function in mouse, it is not required in Drosophila dMarf1. The OST domain is present in the proteins of several species ranging from bacteria to humans. Drosophila melanogaster has has four members of OST domain-containing proteins: dMarf1, Oskar (Osk), Tejas (Tej), and Tapas (Tap). All of these proteins except dMarf1 contain a single OST domain, and are predominantly expressed in germline cells. Structural and biochemical studies of Osk, Tej, and Tap OST domains have revealed the ability of this domain to bind to Vasa, an RNA helicase expressed exclusively in germline cells. Interestingly, the OST domain(s) of MARF1 family members is smaller than those of other proteins and does not bind to Vasa. Instead, a recent study reported that dMarf1 could bind to CCR4-Not deadenylase complex via the OST domain(s); however, the importance and cooperation between multiple OST domains remains elusive. In addition to these two domains, the MARF1 family members contain one or two RRM domains. This study showed that dMarf1 translationally repressed nos mRNA. nos may not be the only target of dMarf1; other mRNAs such as tra2 and abo can also be targeted by dMarf1, although the biological significance of these interactions remains unclear. Zhu has recently reported that dMarf1 can bind to cyclin A mRNA via its RRM domain (Zhu, 2018). However, RNA-IP analysis did not detect cyclin A in the dMarf1-bound mRNA fraction. Further studies of the molecular mechanism underlying the specificity of dMarf1 RNA binding will reveal the range of mRNA regulation during oocyte maturation (Kawaguchi, 2020).
The C-terminal region of the MARF1 family members is highly conserved among higher animals, except insects, despite not forming any secondary structure. The C-terminal region of human MARF1 has been shown to directly interact with the decapping complex component Ge-1; however, this interaction was not observed in Drosophila. Moreover, the C-terminal region of the MARF1 family members is conserved among different insect species, but different from that of higher animals, indicating that it may bind to a unique partner in insects. This hypothesis was supported by results showing that transgenic dMarf1 mutant lacking 47 C-terminal residues (ΔC47) could not rescue dMarf1KO321 mutant phenotype (Kawaguchi, 2020).
In addition to binding to the RNA decapping complex subunit (Block; 2014; Nishimura; 2018), human MARF1 can localize to processing body (P-body), which is often related to translational repression and mRNA decay. Mouse MARF1 has also been shown to degrade target mRNA via its NYN domain, which is absent in Drosophila dMarf1. Transcriptome analysis of mouse MARF1 mutant oocytes revealed that 1,470 transcripts were upregulated in the steady state, whereas 103 transcripts were downregulated, indicating a global impact on RNA homeostasis in the mutant oocytes. By contrast, the expression of a few RNAs was downregulated and dp1 mRNA expression was upregulated in Drosophila dMarf1 mutant ovaries. These results suggest that mammalian MARF1 may regulate the global transcriptome predominantly by degradation, while dMarf1 represses translation of target proteins such as CycB and CycA by modulating Nos/Pumilio and the CCR4-NOT deadenylase complex, respectively (Kawaguchi, 2020).
In addition to nos mRNA, dMarf1 can bind to other mRNAs, including tra2 and abo. The mRNA expression of tra2 was not significantly affected in stage 14 dMarf1KO312 egg chambers, suggesting that dMarf1 post-transcriptionally regulates tra2 expression. abo is a negative regulator of histone gene expression and its expression is downregulated in mature oocytes to produce more histones. The expression of abo mRNA was upregulated by approximately three-fold in stage 14 dMarf1KO312 egg chambers. This may result in the overexpression of Abo protein in dMarf1 mutant oocytes, which in turn causes the downregulation of histone proteins that are required for embryogenesis (Kawaguchi, 2020).
The Ppp2cb gene encodes a protein phosphatase that is involved in cell cycle regulation. Ppp2cb has been previously reported as a major downstream effector of mouse MARF1. The high expression of Ppp2CB phosphatase in the MARF1 mutant ovaries of mouse can disrupt meiosis. However, the expression of mts, a Drosophila homolog of Ppp2cb, was not affected in dMarf1 mutant ovaries, suggesting that the signaling pathway for the activation of the M phase promoting factor, CycB/Cdk1, is not conserved between mouse and Drosophila. Although the direct activation of MPF in mouse MARF1 mutant oocytes by the inhibition of Ppp2cb rescued meiotic defect, embryogenesis of mutant oocytes was affected, suggesting that Ppp2cb may have additional functions in addition to MPF activation. Similarly, dMarf1KO312 ovaries exhibited not only meiotic defects, but also translationally downregulated some proteins required for embryogenesis, such as Dhd and Gnu. In conclusion, MARF1 may trigger oocyte maturation and coordinate multiple events during late oogenesis and fertilization (Kawaguchi, 2020).
EDC4 is a core component of processing (P)-bodies that binds the DCP2 decapping enzyme and stimulates mRNA decay. EDC4 also interacts with mammalian MARF1, a recently identified endoribonuclease that promotes oogenesis and contains a number of RNA binding domains, including two RRMs and multiple LOTUS domains. How EDC4 regulates MARF1 action and the identity of MARF1 target mRNAs is not known. Transcriptome-wide analysis identifies bona fide MARF1 target mRNAs and indicates that MARF1 predominantly binds their 3' UTRs via its LOTUS domains to promote their decay. This study also shows that a MARF1 RRM plays an essential role in enhancing its endonuclease activity. Importantly, it was established that EDC4 impairs MARF1 activity by preventing its LOTUS domains from binding target mRNAs. Thus, EDC4 not only serves as an enhancer of mRNA turnover that binds DCP2, but also as a repressor that binds MARF1 to prevent the decay of MARF1 target mRNAs (Brothers, 2020).
Meiosis arrest female 1 (MARF1) is a cytoplasmic RNA binding protein that is essential for meiotic progression of mouse oocytes, in part by limiting retrotransposon expression. MARF1 is also expressed in somatic cells and tissues; however, its mechanism of action has yet to be investigated. Human MARF1 contains a NYN-like domain, two RRMs and eight LOTUS domains. This study provides evidence that MARF1 post-transcriptionally silences targeted mRNAs. MARF1 physically interacts with the DCP1:DCP2 mRNA decapping complex but not with deadenylation machineries. Importantly, this study provide a 1.7 Å resolution crystal structure of the human MARF1 NYN domain, which is demonstrated to be a bona fide endoribonuclease, the activity of which is essential for the repression of MARF1-targeted mRNAs. Thus, MARF1 post-transcriptionally represses gene expression by serving as both an endoribonuclease and as a platform that recruits the DCP1:DCP2 decapping complex to targeted mRNAs (Nishimura, 2018).
Producing normal eggs for fertilization and species propagation requires completion of meiosis and protection of the genome from the ravages of retrotransposons. Mutation of Marf1 (meiosis regulator and mRNA stability factor 1) results in defects in both these key processes in mouse oocytes and thus in infertility. MARF1 was predicted to have ribonuclease activity, but the structural basis for the function of MARF1 and the contribution of its putative ribonuclease domain to the mutant oocyte phenotype was unknown. Therefore, this study resolved the crystal structures of key domains of MARF1 and demonstrated by biochemical and mutagenic analyses that the ribonuclease activity of MARF1 controls oocyte meiotic progression and retrotransposon surveillance. The N-terminal NYN domain of MARF1 resembles the nuclease domains of Vpa0982, T4 RNase H, and MCPIP1 and contains four conserved aspartate residues, D178, D215, D246, and D272. The C-terminal LOTUS domain of MARF1 adopts a winged helix-turn-helix fold and binds ssRNA and dsRNA. Purified MARF1 cleaved ssRNAs in vitro, but this cleavage activity was abolished by mutations of conserved aspartates in its NYN domain and truncation of the LOTUS domain. Furthermore, a point mutation in the D272 residue in vivo caused a female-only infertile phenotype in mice, with failure of meiotic resumption and elevation of Line1 and Iap retrotransposon transcripts and DNA double-strand breaks in oocytes. Therefore, the ribonuclease activity of MARF1 controls oocyte meiosis and genome integrity. This activity depends upon conserved aspartic residues in the catalytic NYN domain and the RNA-binding activity of the LOTUS domain (Yao, 2018).
The mRNA processing body (P-body) is a cellular structure that regulates the stability of cytoplasmic mRNA. MARF1 is a murine oocyte RNA-binding protein that is associated with maintenance of mRNA homeostasis and genomic stability. In this study, autoantibodies were used to identify Limkain B (LMKB), the human orthologue of MARF1, as a P-body component. Indirect immunofluorescence demonstrated that Ge-1 (a central component of the mammalian core-decapping complex) co-localized with LMKB in P-bodies. Two-hybrid and co-immunoprecipitation assays were used to demonstrate interaction between Ge-1 and LMKB. The C-terminal 120 amino acids of LMKB mediated interaction with Ge-1 and the N-terminal 1094 amino acids of Ge-1 were required for interaction with LMKB. LMKB is the first protein identified to date that interacts with this portion of Ge-1. LMKB was expressed in human B and T lymphocyte cell lines; depletion of LMKB increased expression of IFI44L, a gene that has been implicated in the cellular response to Type I interferons. The interaction between LMKB/MARF1, a protein that contains RNA-binding domains, and Ge-1, which interacts with core-decapping proteins, suggests that LMKB has a role in the regulation of mRNA stability. LMKB appears to have different functions in different cell types: maintenance of genomic stability in developing oocytes and possible dampening of the inflammatory response in B and T cells (Bloch, 2014).
Development of fertilization-competent oocytes depends on integrated processes controlling meiosis, cytoplasmic development, and maintenance of genomic integrity. This study shows that meiosis arrest female 1 (MARF1) is required for these processes in mammalian oocytes. Mutations of Marf1 cause female infertility characterized by up-regulation of a cohort of transcripts, increased retrotransposon expression, defective cytoplasmic maturation, and meiotic arrest. Up-regulation of protein phosphatase 2 catalytic subunit (PPP2CB) is key to the meiotic arrest phenotype. Moreover, Iap and Line1 retrotransposon messenger RNAs are also up-regulated, and, concomitantly, DNA double-strand breaks are elevated in mutant oocytes. Therefore MARF1, by suppressing levels of specific transcripts, is an essential regulator of important oogenic processes leading to female fertility and the development of healthy offspring (Su, 2012a).
Orderly regulation of meiosis and protection of germline genomic integrity from transposable elements are essential for male and female gamete development. In the male germline, these processes are ensured by proteins associated with cytoplasmic nuage, but morphologically similar germ granules or nuage have not been identified in mammalian female germ cells. Indeed, many mutations affecting nuage-associated proteins such as PIWI and tudor domain containing proteins 5 and 7 (TDRD5/7) can result in failure of meiosis, up-regulation of retrotransposons, and infertility only in males and not in females. MARF1 (meiosis arrest female 1) has been identified as a protein essential for controlling meiosis and retrotransposon surveillance in oocytes; and in contrast to PIWI-pathway mutations, Marf1 mutant females are infertile, whereas mutant males are fertile. This study put forward the hypothesis that MARF1 in mouse oocytes is a functional counterpart of the nuage-associated components of spermatocytes. The developmental pattern is described of Marf1 expression and its roles in retrotransposon silencing and protection from DNA double-strand breaks. Analysis of MARF1 protein domains compared with PIWI and TDRD5/7 revealed that these functional similarities are reflected in remarkable structural analogies. Thus, functions that in the male germline require protein interactions and cooperative scaffolding are combined in MARF1, allowing a single molecule to execute crucial activities of meiotic regulation and protection of germline genomic integrity (Su, 2012b).
Search PubMed for articles about Drosophila Marf1
Bloch, D. B., Li, P., Bloch, E. G., Berenson, D. F., Galdos, R. L., Arora, P., Malhotra, R., Wu, C. and Yang, W. (2014). LMKB/MARF1 localizes to mRNA processing bodies, interacts with Ge-1, and regulates IFI44L gene expression. PLoS One 9(4): e94784. PubMed ID: 24755989
Brothers, W. R., Hebert, S., Kleinman, C. L. and Fabian, M. R. (2020). A non-canonical role for the EDC4 decapping factor in regulating MARF1-mediated mRNA decay. Elife 9. PubMed ID: 32510323
Kawaguchi, S., Ueki, M. and Kai, T. (2020). Drosophila MARF1 ensures proper oocyte maturation by regulating nanos expression. PLoS One 15(4): e0231114. PubMed ID: 32243476
Nishimura, T., Fakim, H., Brandmann, T., Youn, J. Y., Gingras, A. C., Jinek, M. and Fabian, M. R. (2018). Human MARF1 is an endoribonuclease that interacts with the DCP1:2 decapping complex and degrades target mRNAs. Nucleic Acids Res 46(22): 12008-12021. PubMed ID: 30364987
Su, Y. Q., Sugiura, K., Sun, F., Pendola, J. K., Cox, G. A., Handel, M. A., Schimenti, J. C. and Eppig, J. J. (2012a). MARF1 regulates essential oogenic processes in mice. Science 335(6075): 1496-1499. PubMed ID: 22442484
Su, Y. Q., Sun, F., Handel, M. A., Schimenti, J. C. and Eppig, J. J. (2012b). Meiosis arrest female 1 (MARF1) has nuage-like function in mammalian oocytes. Proc Natl Acad Sci U S A 109(46): 18653-18660. PubMed ID: 23090997
Yao, Q., Cao, G., Li, M., Wu, B., Zhang, X., Zhang, T., Guo, J., Yin, H., Shi, L., Chen, J., Yu, X., Zheng, L., Ma, J. and Su, Y. Q. (2018). Ribonuclease activity of MARF1 controls oocyte RNA homeostasis and genome integrity in mice. Proc Natl Acad Sci U S A 115(44): 11250-11255. PubMed ID: 30333187
Zhu, L., Kandasamy, S. K., Liao, S. E. and Fukunaga, R. (2018). LOTUS domain protein MARF1 binds CCR4-NOT deadenylase complex to post-transcriptionally regulate gene expression in oocytes. Nat Commun 9(1): 4031. PubMed ID: 30279526
date revised: 20 November 2020
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