SR protein

File:SR proteins competing with hnRNPs.png

SR protein
Identifiers
Symbol	?

SR proteins are a family of RNA-binding proteins that play a crucial role in the splicing of pre-mRNA in eukaryotic cells. These proteins are characterized by the presence of one or two RNA recognition motifs (RRMs) at their N-terminus and a serine/arginine-rich (SR) domain at their C-terminus. The SR domain is essential for protein-protein interactions and is heavily phosphorylated, which regulates the activity of SR proteins.

Function

SR proteins are primarily involved in the alternative splicing of pre-mRNA, a process that allows a single gene to produce multiple protein isoforms. They function by binding to specific sequences on the pre-mRNA and recruiting the spliceosome components to the correct splice sites. This ensures the accurate removal of introns and the joining of exons to form mature mRNA.

In addition to their role in splicing, SR proteins are also involved in other aspects of RNA metabolism, including mRNA export, mRNA stability, and translation.

Structure

The structure of SR proteins typically includes:

• One or two RNA recognition motifs (RRMs) at the N-terminus, which are responsible for binding to RNA.
• A serine/arginine-rich (SR) domain at the C-terminus, which mediates protein-protein interactions and is subject to extensive phosphorylation.

Regulation

The activity of SR proteins is regulated by phosphorylation. Specific kinases, such as SRPK1 and CLK1, phosphorylate the SR domain, which influences the protein's ability to interact with other splicing factors and RNA. Dephosphorylation by specific phosphatases can reverse these modifications, thereby modulating the function of SR proteins.

Clinical Significance

Mutations or dysregulation of SR proteins have been implicated in various diseases, including cancer, neurodegenerative diseases, and genetic disorders. For example, alterations in the expression or function of SR proteins can lead to aberrant splicing patterns, which may contribute to the development and progression of these diseases.

Examples of SR Proteins

Some well-known members of the SR protein family include:

• SRSF1 (also known as ASF/SF2)
• SRSF2 (also known as SC35)
• SRSF3 (also known as SRp20)
• SRSF4 (also known as SRp75)

See Also

• Spliceosome
• Alternative splicing
• RNA-binding protein
• mRNA export
• Phosphorylation