SR protein

SR proteins translocating out of the nucleus with TAP

File:SR proteins competing with hnRNPs.png

SR proteins and hnRNPs

Serine/arginine-rich (SR) proteins are a family of proteins involved in the regulation of gene expression by influencing RNA splicing. These proteins are characterized by their serine/arginine-rich domains, which facilitate their interaction with RNA and other components of the splicing machinery. SR proteins play a crucial role in both constitutive splicing and alternative splicing, thereby influencing the diversity of mRNA transcripts produced from a single gene.

Function

SR proteins are essential for the splicing of pre-mRNA into mature mRNA in eukaryotic cells. They bind to specific sequences on the pre-mRNA and recruit the components of the spliceosome, the complex responsible for removing introns and joining exons. By influencing the selection of splice sites, SR proteins can regulate alternative splicing, a process that allows a single gene to produce multiple forms of mRNA and, consequently, different protein isoforms. This regulation is vital for the development, differentiation, and response to environmental stimuli in eukaryotic organisms.

Structure

The defining feature of SR proteins is the presence of one or two RNA recognition motifs (RRMs) at their N-terminus and a domain rich in serine and arginine residues (the RS domain) at their C-terminus. The RRMs are responsible for binding RNA, while the RS domain mediates protein-protein interactions, particularly with other components of the splicing machinery. The RS domain is also involved in the regulation of protein localization and function through phosphorylation.

Types and Examples

There are several types of SR proteins, each with specific roles in splicing regulation. Some well-known examples include:

• SRSF1 (Serine/Arginine-Rich Splicing Factor 1), which influences the selection of alternative 5' splice sites.
• SRSF2 (Serine/Arginine-Rich Splicing Factor 2), involved in exon recognition and splice site selection.
• SRSF3 (Serine/Arginine-Rich Splicing Factor 3), which has a role in both constitutive and alternative splicing.

Role in Disease

Alterations in the expression or function of SR proteins can lead to aberrant splicing and the production of dysfunctional proteins, contributing to the development of various diseases, including cancer, neurodegenerative diseases, and spinal muscular atrophy. For example, changes in the expression levels of SRSF1 have been implicated in the progression of certain types of cancer.

Research and Therapeutic Potential

Understanding the mechanisms by which SR proteins regulate splicing is of significant interest in biomedical research. Modulating the activity of specific SR proteins offers a potential therapeutic strategy for diseases caused by splicing defects. For instance, compounds that influence the phosphorylation state of SR proteins could be used to correct aberrant splicing patterns in disease conditions.