SR protein

SR proteins are serine/arginine-rich proteins which are involved in regulating and selecting splice sites in eukaryotic mRNA. Alternative splicing requires SR proteins, which select the alternative splice sites to be utilized. SR proteins also play a role in constitutive splicing--that is, with mRNAs that are always spliced the same way.

SR proteins may work in an antagonistic fashion, competing with each other in binding to exonic splicing enhancers. Some evidence suggests that selection of the mRNA splicing variant depends upon the relative ratios of SR proteins.

These proteins generally have two domains: an RS domain, rich in Arginine-Serine repeats; and an RNA-recognition motif (RRM). The RS domain is subject to serine phosphorylation, which seems to control interactions with other proteins (including other SR proteins). The RRM seems to recognize specific RNA sequences, typically located within exons. Other splicing factors may also contain an RS domain; these are referred to as SR-related proteins.

In 1990, Mark Roth, working as a postdoctoral fellow with Joseph Gall, discovered an antibody, mAb104, which binds to active sites of RNA polymerase II transcription. This antibody allowed identification of four SR proteins (SRp20, SRp40, SRp55 and SRp75) and demonstrated their conservation among vertebrates and invertebrates. They were named SR proteins because they contained long repeats of serine and arginine, the amino acid abbreviations of which are "S" and "R".

RNAi knockdown of SR proteins seems to give no detectable phenotype in C. elegans, except SF2/ASF, which is essential in the embryonic phase of development. It is likely that SR proteins have overlapping function; in other words, when one is missing another can make up for it. In mice, knockouts of SR protein-coding genes results in an embryonic lethal phenotype. There is some possibility that the discrepancy between mice and C. elegans is due to remaining low levels of SR proteins (characteristic of RNAi knockdowns). Some cell types, however, seem not to require SR proteins.

Location and translocation

SR proteins are often localized in nuclear speckles in the nucleus based on phosphorylation of the RS domain. Some SR proteins travel between the nucleus and the cytoplasm, a process which also seems to be controlled by phosphorylation state. Recent studies (in 2006) suggest fundamental differences in the regulation of the mobility of plant (ATP dependent) and animal (ATP independent) SR splicing factors.

Function

SR proteins have been shown to have roles in alternative and constitutive splicing in addition to roles in translation.

Exon dependent roles (splicing)

• Recruitment of U1 and U2AF
• Splicing regulatory functions

Exon independent roles (splicing)

• SR protein may have a role in recruiting U₄U₅U₆ tri-complex.

References

• Graveley BR (September 2000). "Sorting out the complexity of SR protein functions". RNA 6 (9): 1197–211. doi:10.1017/S1355838200000960. PMC 1369994. PMID 10999598. http://www.rnajournal.org/cgi/pmidlookup?view=long&pmid=10999598.