Both loss-of-function and gain-of-function mutations in snf define a role for snRNP proteins in regulating Sex-lethal pre-mRNA splicing in Drosophila development - PubMed (original) (raw)
Both loss-of-function and gain-of-function mutations in snf define a role for snRNP proteins in regulating Sex-lethal pre-mRNA splicing in Drosophila development
H K Salz et al. Genetics. 1996 Sep.
Abstract
The Drosophila snf gene encodes a protein with functional homology to the mammalian U1A and U2B" snRNP proteins. Studies, based on the analysis of three viable alleles, have suggested a role for snf in establishing the female-specific splicing pattern of the sex determination switch gene, sex-lethal. Here, we show that the non-sex-specific lethal null allele is required for female sex determination, arguing against the formal possibility that the viable alleles disrupt a function unrelated to snf's wild-type function. Moreover, we find snf is required for normal cell growth and/or survival, as expected for a protein involved in a cell-vital process such as RNA splicing. We also show that of the three viable alleles only one, snfJA2, is a partial loss-of-function mutation. The other two viable alleles, snf1621 and snfe8H, encode antimorphic proteins. We find the antimorphic proteins are mislocalized and correlate their mislocalization with their molecular lesions and mutant phenotypes. Finally, we provide genetic evidence that the antimorphic alleles interfere with the autoregulatory splicing function of the Sex-lethal protein. Based on these studies we suggest a model in which the snRNP protein, Snf, functions with Sex-lethal to block recognition of the regulated male-specific exon.
Similar articles
- Functioning of the Drosophila integral U1/U2 protein Snf independent of U1 and U2 small nuclear ribonucleoprotein particles is revealed by snf(+) gene dose effects.
Cline TW, Rudner DZ, Barbash DA, Bell M, Vutien R. Cline TW, et al. Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14451-8. doi: 10.1073/pnas.96.25.14451. Proc Natl Acad Sci U S A. 1999. PMID: 10588726 Free PMC article. - Functional analysis of SNF, the Drosophila U1A/U2B" homolog: identification of dispensable and indispensable motifs for both snRNP assembly and function in vivo.
Stitzinger SM, Conrad TR, Zachlin AM, Salz HK. Stitzinger SM, et al. RNA. 1999 Nov;5(11):1440-50. doi: 10.1017/s1355838299991306. RNA. 1999. PMID: 10580472 Free PMC article. - RNA binding protein sex-lethal (Sxl) and control of Drosophila sex determination and dosage compensation.
Penalva LO, Sánchez L. Penalva LO, et al. Microbiol Mol Biol Rev. 2003 Sep;67(3):343-59, table of contents. doi: 10.1128/MMBR.67.3.343-359.2003. Microbiol Mol Biol Rev. 2003. PMID: 12966139 Free PMC article. Review. - Sex, AGility, and the regulation of alternative splicing.
Graveley BR. Graveley BR. Cell. 2002 May 17;109(4):409-12. doi: 10.1016/s0092-8674(02)00750-x. Cell. 2002. PMID: 12086596 Review.
Cited by
- An N-terminal truncation uncouples the sex-transforming and dosage compensation functions of sex-lethal.
Yanowitz JL, Deshpande G, Calhoun G, Schedl PD. Yanowitz JL, et al. Mol Cell Biol. 1999 Apr;19(4):3018-28. doi: 10.1128/MCB.19.4.3018. Mol Cell Biol. 1999. PMID: 10082569 Free PMC article. - Functioning of the Drosophila integral U1/U2 protein Snf independent of U1 and U2 small nuclear ribonucleoprotein particles is revealed by snf(+) gene dose effects.
Cline TW, Rudner DZ, Barbash DA, Bell M, Vutien R. Cline TW, et al. Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14451-8. doi: 10.1073/pnas.96.25.14451. Proc Natl Acad Sci U S A. 1999. PMID: 10588726 Free PMC article. - Trans-acting factors required for inclusion of regulated exons in the Ultrabithorax mRNAs of Drosophila melanogaster.
Burnette JM, Hatton AR, Lopez AJ. Burnette JM, et al. Genetics. 1999 Apr;151(4):1517-29. doi: 10.1093/genetics/151.4.1517. Genetics. 1999. PMID: 10101174 Free PMC article. - Promiscuity in post-transcriptional control of gene expression: Drosophila sex-lethal and its regulatory partnerships.
Moschall R, Gaik M, Medenbach J. Moschall R, et al. FEBS Lett. 2017 Jun;591(11):1471-1488. doi: 10.1002/1873-3468.12652. Epub 2017 Apr 28. FEBS Lett. 2017. PMID: 28391641 Free PMC article. Review. - Functioning of the Drosophila Wilms'-tumor-1-associated protein homolog, Fl(2)d, in Sex-lethal-dependent alternative splicing.
Penn JK, Graham P, Deshpande G, Calhoun G, Chaouki AS, Salz HK, Schedl P. Penn JK, et al. Genetics. 2008 Feb;178(2):737-48. doi: 10.1534/genetics.107.081679. Epub 2008 Feb 3. Genetics. 2008. PMID: 18245840 Free PMC article.
References
- Proc Natl Acad Sci U S A. 1971 Sep;68(9):2222-6 - PubMed
- Genes Dev. 1993 Mar;7(3):419-28 - PubMed
- Genetics. 1984 Jun;107(2):231-77 - PubMed
- Genetics. 1987 Oct;117(2):221-31 - PubMed
- Genes Dev. 1988 Jun;2(6):754-65 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases