Abstract
Cell fates in the Caenorhabditis elegans germline are regulated, at least in part, at the posttranscriptional level. For example, the switch from spermatogenesis to oogenesis in the hermaphrodite relies on posttranscriptional repression of the fem-3 mRNA via its 3' untranslated region (UTR). Previous studies identified three DEAH box proteins, MOG-1, MOG-4, and MOG-5, that are critical for the fem-3 3' UTR control. Here we describe MEP-1, a zinc-finger protein that binds specifically to each of these three MOG proteins and that is required for repression by the fem-3 3' UTR in vivo. To investigate its in vivo function, we generated a mep-1 deletion mutant. The mep-1 null phenotype suggests a broad role for MEP-1 in C. elegans development, as it is associated with early larval arrest. In addition, mep-1 mutants can be defective in gonadogenesis and oocyte production when derived from a heterozygous mother. We suggest that MEP-1 acts together with the MOG proteins to repress fem-3 mRNA and that it also functions in other pathways to control development more broadly.
Full Text
The Full Text of this article is available as a PDF (4.5 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ahringer J., Kimble J. Control of the sperm-oocyte switch in Caenorhabditis elegans hermaphrodites by the fem-3 3' untranslated region. Nature. 1991 Jan 24;349(6307):346–348. doi: 10.1038/349346a0. [DOI] [PubMed] [Google Scholar]
- Austin J., Kimble J. glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans. Cell. 1987 Nov 20;51(4):589–599. doi: 10.1016/0092-8674(87)90128-0. [DOI] [PubMed] [Google Scholar]
- Barton M. K., Schedl T. B., Kimble J. Gain-of-function mutations of fem-3, a sex-determination gene in Caenorhabditis elegans. Genetics. 1987 Jan;115(1):107–119. doi: 10.1093/genetics/115.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bettinger J. C., Lee K., Rougvie A. E. Stage-specific accumulation of the terminal differentiation factor LIN-29 during Caenorhabditis elegans development. Development. 1996 Aug;122(8):2517–2527. doi: 10.1242/dev.122.8.2517. [DOI] [PubMed] [Google Scholar]
- Blelloch R., Anna-Arriola S. S., Gao D., Li Y., Hodgkin J., Kimble J. The gon-1 gene is required for gonadal morphogenesis in Caenorhabditis elegans. Dev Biol. 1999 Dec 1;216(1):382–393. doi: 10.1006/dbio.1999.9491. [DOI] [PubMed] [Google Scholar]
- Chen J. H., Lin R. J. The yeast PRP2 protein, a putative RNA-dependent ATPase, shares extensive sequence homology with two other pre-mRNA splicing factors. Nucleic Acids Res. 1990 Nov 11;18(21):6447–6447. doi: 10.1093/nar/18.21.6447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Company M., Arenas J., Abelson J. Requirement of the RNA helicase-like protein PRP22 for release of messenger RNA from spliceosomes. Nature. 1991 Feb 7;349(6309):487–493. doi: 10.1038/349487a0. [DOI] [PubMed] [Google Scholar]
- Evans T. C., Crittenden S. L., Kodoyianni V., Kimble J. Translational control of maternal glp-1 mRNA establishes an asymmetry in the C. elegans embryo. Cell. 1994 Apr 22;77(2):183–194. doi: 10.1016/0092-8674(94)90311-5. [DOI] [PubMed] [Google Scholar]
- Fire A., Albertson D., Harrison S. W., Moerman D. G. Production of antisense RNA leads to effective and specific inhibition of gene expression in C. elegans muscle. Development. 1991 Oct;113(2):503–514. doi: 10.1242/dev.113.2.503. [DOI] [PubMed] [Google Scholar]
- Fire A., Xu S., Montgomery M. K., Kostas S. A., Driver S. E., Mello C. C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998 Feb 19;391(6669):806–811. doi: 10.1038/35888. [DOI] [PubMed] [Google Scholar]
- Gallegos M., Ahringer J., Crittenden S., Kimble J. Repression by the 3' UTR of fem-3, a sex-determining gene, relies on a ubiquitous mog-dependent control in Caenorhabditis elegans. EMBO J. 1998 Nov 2;17(21):6337–6347. doi: 10.1093/emboj/17.21.6337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goodwin E. B., Okkema P. G., Evans T. C., Kimble J. Translational regulation of tra-2 by its 3' untranslated region controls sexual identity in C. elegans. Cell. 1993 Oct 22;75(2):329–339. doi: 10.1016/0092-8674(93)80074-o. [DOI] [PubMed] [Google Scholar]
- Goodwin EB, Evans TC. Translational control of development in C. elegans. Semin Cell Dev Biol. 1997 Dec;8(6):551–559. doi: 10.1006/scdb.1997.0180. [DOI] [PubMed] [Google Scholar]
- Graham P. L., Kimble J. The mog-1 gene is required for the switch from spermatogenesis to oogenesis in Caenorhabditis elegans. Genetics. 1993 Apr;133(4):919–931. doi: 10.1093/genetics/133.4.919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Graham P. L., Schedl T., Kimble J. More mog genes that influence the switch from spermatogenesis to oogenesis in the hermaphrodite germ line of Caenorhabditis elegans. Dev Genet. 1993;14(6):471–484. doi: 10.1002/dvg.1020140608. [DOI] [PubMed] [Google Scholar]
- Hodgkin J. Sex determination in the nematode C. elegans: analysis of tra-3 suppressors and characterization of fem genes. Genetics. 1986 Sep;114(1):15–52. doi: 10.1093/genetics/114.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kimble J., Hirsh D. The postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans. Dev Biol. 1979 Jun;70(2):396–417. doi: 10.1016/0012-1606(79)90035-6. [DOI] [PubMed] [Google Scholar]
- Kraemer B., Crittenden S., Gallegos M., Moulder G., Barstead R., Kimble J., Wickens M. NANOS-3 and FBF proteins physically interact to control the sperm-oocyte switch in Caenorhabditis elegans. Curr Biol. 1999 Sep 23;9(18):1009–1018. doi: 10.1016/s0960-9822(99)80449-7. [DOI] [PubMed] [Google Scholar]
- Lee R. C., Feinbaum R. L., Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993 Dec 3;75(5):843–854. doi: 10.1016/0092-8674(93)90529-y. [DOI] [PubMed] [Google Scholar]
- McCarter J., Bartlett B., Dang T., Schedl T. Soma-germ cell interactions in Caenorhabditis elegans: multiple events of hermaphrodite germline development require the somatic sheath and spermathecal lineages. Dev Biol. 1997 Jan 15;181(2):121–143. doi: 10.1006/dbio.1996.8429. [DOI] [PubMed] [Google Scholar]
- Mickey K. M., Mello C. C., Montgomery M. K., Fire A., Priess J. R. An inductive interaction in 4-cell stage C. elegans embryos involves APX-1 expression in the signalling cell. Development. 1996 Jun;122(6):1791–1798. doi: 10.1242/dev.122.6.1791. [DOI] [PubMed] [Google Scholar]
- Moss E. G., Lee R. C., Ambros V. The cold shock domain protein LIN-28 controls developmental timing in C. elegans and is regulated by the lin-4 RNA. Cell. 1997 Mar 7;88(5):637–646. doi: 10.1016/s0092-8674(00)81906-6. [DOI] [PubMed] [Google Scholar]
- Puoti A., Kimble J. The Caenorhabditis elegans sex determination gene mog-1 encodes a member of the DEAH-Box protein family. Mol Cell Biol. 1999 Mar;19(3):2189–2197. doi: 10.1128/mcb.19.3.2189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Puoti A., Kimble J. The hermaphrodite sperm/oocyte switch requires the Caenorhabditis elegans homologs of PRP2 and PRP22. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3276–3281. doi: 10.1073/pnas.97.7.3276. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwer B., Guthrie C. PRP16 is an RNA-dependent ATPase that interacts transiently with the spliceosome. Nature. 1991 Feb 7;349(6309):494–499. doi: 10.1038/349494a0. [DOI] [PubMed] [Google Scholar]
- SenGupta D. J., Zhang B., Kraemer B., Pochart P., Fields S., Wickens M. A three-hybrid system to detect RNA-protein interactions in vivo. Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8496–8501. doi: 10.1073/pnas.93.16.8496. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Slack F. J., Basson M., Liu Z., Ambros V., Horvitz H. R., Ruvkun G. The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor. Mol Cell. 2000 Apr;5(4):659–669. doi: 10.1016/s1097-2765(00)80245-2. [DOI] [PubMed] [Google Scholar]
- Tzoumaris ITh Aktinographikos prosanatolismos egkleiston sophronisteron tes kato gnathou os kai schesis auton oson aphora ten demiourgian kentrikon ogkon ten periochen tou egklobismou. Stoma (Thessaloniki) 1969 Mar-Apr;1(2):100–111. [PubMed] [Google Scholar]
- White F. M. Family history of allergy and skin test reactivity. Can Med Assoc J. 1985 Jul 1;133(1):15–16. [PMC free article] [PubMed] [Google Scholar]
- Zhang B., Gallegos M., Puoti A., Durkin E., Fields S., Kimble J., Wickens M. P. A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line. Nature. 1997 Dec 4;390(6659):477–484. doi: 10.1038/37297. [DOI] [PubMed] [Google Scholar]
- van Nues R. W., Beggs J. D. Functional contacts with a range of splicing proteins suggest a central role for Brr2p in the dynamic control of the order of events in spliceosomes of Saccharomyces cerevisiae. Genetics. 2001 Apr;157(4):1451–1467. doi: 10.1093/genetics/157.4.1451. [DOI] [PMC free article] [PubMed] [Google Scholar]