SR protein
Encyclopedia
SR proteins are serine
/arginine
-rich protein
s 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 embryo
nic 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.
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.
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
/arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
-rich protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s which are involved in regulating and selecting splice sites
Splicing (genetics)
In molecular biology and genetics, splicing is a modification of an RNA after transcription, in which introns are removed and exons are joined. This is needed for the typical eukaryotic messenger RNA before it can be used to produce a correct protein through translation...
in eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
mRNA. Alternative splicing
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA 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
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
, 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
Mark Roth (scientist)
Mark Roth is an American biochemist, and director of the Roth Lab at the Fred Hutchinson Cancer Research Center. He is a professor at the University of Washington....
, working as a postdoctoral fellow with Joseph Gall
Joseph G. Gall
Joseph Grafton Gall is an American cell biologist and winner of the 2006 Albert Lasker Special Achievement Award. He also won the 2007 Louisa Gross Horwitz Prize...
, 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
RNAI
RNAI is a non-coding RNA that is an antisense repressor of the replication of some E. coli plasmids, including ColE1. Plasmid replication is usually initiated by RNAII, which acts as a primer by binding to its template DNA. The complementary RNAI binds RNAII prohibiting it from its initiation role...
knockdown of SR proteins seems to give no detectable phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
in C. elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...
, except SF2/ASF, which is essential in the embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
nic 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 nucleusCell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
based on phosphorylation of the RS domain. Some SR proteins travel between the nucleus and the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within 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 independent roles (splicing)
- SR protein may have a role in recruiting U4U5U6 tri-complex.