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PMID: 15961996 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Negative feedback regulation among SR splicing factors encoded by Rbp1 and Rbp1-like in Drosophila.

The EMBO journal ·Vol. 24 ·No. 14 ·2005-07-20 ·Pages 2646-55

Kumar S, Lopez AJ

Abstract

SR proteins constitute a widely conserved family of splicing regulators. Negative autoregulation of SR proteins has been proposed to exert homeostatic control on the splicing environment, but few examples have been studied and the role of isoforms that lack the RS domain is unclear. We show that genes Rbp1 and Rbp1-like, which encode Drosophila homologs of mammalian SRp20, negatively autoregulate and crossregulate at the level of alternative 3' splice site selection. This adjusts the relative expression of isoforms with either an RS domain or unrelated C-terminal domains (ALT) that are rich in serine and threonine. The effects of RBP1-ALT on splicing of doublesex and Rbp1-like are opposite to those of RBP1-RS and RBP1L-RS. RBP1-ALT and -RS exert opposing negative feedback on the ALT/RS ratio. However, RBP1-ALT inhibits the expression of RBP1-RS while stimulating that of RBP1L-RS. This asymmetry may contribute to changes in the RBP1-RS/RBP1L-RS ratio that are observed during development. These results provide the first example of a feedback-regulated SR protein network with evidence of an active homeostatic role for alternative isoforms.

MeSH Terms
3' Untranslated Regions/physiology Alternative Splicing/physiology Animals Cell Line Down-Regulation/physiology Drosophila/genetics,metabolism Drosophila Proteins/biosynthesis,genetics,metabolism,physiology Feedback, Physiological/physiology Nuclear Proteins/biosynthesis,genetics Protein Isoforms/genetics,metabolism,physiology RNA Splicing Factors RNA, Messenger/metabolism RNA-Binding Proteins/genetics,metabolism,physiology Receptor Cross-Talk/physiology Ribonucleoproteins/biosynthesis,genetics
Chemicals
3' Untranslated Regions Drosophila Proteins Nuclear Proteins Protein Isoforms RBP1 protein, Drosophila RNA Splicing Factors RNA, Messenger RNA-Binding Proteins Rbp1-like protein, Drosophila Ribonucleoproteins Tra protein, Drosophila tra2 protein, Drosophila
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kumar Supriya
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Lopez A Javier
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600723
Published
2005-07-20
Epub
2005-00-16
Pages
2646-55
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1176452
Subset
IM
Grants
NICHD NIH HHS · K02-HD01155 · United States
NICHD NIH HHS · R01-HD28664 · United States
External Links
PubMed source DOI: 10.1038/sj.emboj.7600723 PMC Full Text View journal details
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