InterPro domain: IPR034143

This entry represents the RNA recognition motif (RRM) of snRNP70 (also known as U1-70K), a key component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome [ 1 ].

U1-70K plays an essential role in targeting the U1 snRNP to the 5' splice site through protein-protein interactions with regulatory RNA-binding splicing factors, such as the RS protein ASF/SF2. It can also specifically bind to stem-loop I of the U1 small nuclear RNA (U1 snRNA) contained in the U1 snRNP complex. It also mediates the binding of U1C, another U1-specific protein, to the U1 snRNP complex [ 2 ].

U1-70K contains a conserved RNA recognition motif (RRM), followed by an adjacent glycine-rich region at the N-terminal half, and two serine/arginine-rich (SR) domains at the C-terminal half. The RRM is responsible for the binding of stem-loop I of U1 snRNA molecule. Additionally, the most prominent immunodominant region that can be recognized by auto-antibodies from autoimmune patients may be located within the RRM. The SR domains are involved in protein-protein interaction with SR proteins that mediate 5' splice site recognition [ 3 ]. For instance, the first SR domain is necessary and sufficient for ASF/SF2 binding [ 4 , 5 ].

Proteins containing this domain also includes Drosophila U1-70K that is an essential splicing factor required for viability in flies, but its SR domain is dispensable [ 6 ].

1. Cloning of the human cDNA for the U1 RNA-associated 70K protein. EMBO J. 5, 3209-17
2. Crystal structure of human spliceosomal U1 snRNP at 5.5 A resolution. Nature 458, 475-80
3. Interaction between the RNA binding domains of Ser-Arg splicing factor 1 and U1-70K snRNP protein determines early spliceosome assembly. Proc. Natl. Acad. Sci. U.S.A. 108, 8233-8
4. A serine/arginine-rich domain in the human U1 70k protein is necessary and sufficient for ASF/SF2 binding. J. Biol. Chem. 273, 20629-35
5. Splicing-independent recruitment of U1 snRNP to a transcription unit in living cells. J. Cell. Sci. 123, 2085-93
6. The Drosophila U1-70K protein is required for viability, but its arginine-rich domain is dispensable. Genetics 168, 2059-65