U1A

U1A (also known as SNRPA) is a small nuclear ribonucleoprotein that forms part of the U1 small nuclear ribonucleoprotein particle (U1 snRNP), a core component of the spliceosome complex responsible for the removal of introns from pre‑messenger RNA in eukaryotic cells. The protein is encoded by the SNRPA gene located on chromosome 19p13.3 in humans and is conserved across a wide range of metazoans.

Structurally, U1A is a 233‑amino‑acid protein that contains two RNA‑recognition motifs (RRMs) at its N‑terminal region. These domains bind specifically to stem‑loop I of the U1 snRNA, stabilizing the snRNP particle and facilitating its assembly. The C‑terminal region interacts with other U1 snRNP proteins, such as U1‑70K and U1C, establishing the architecture required for splice site recognition.

Functionally, U1A contributes to the early steps of spliceosome formation by anchoring the U1 snRNA to the 5′ splice site of pre‑mRNA. In addition to its canonical role in splicing, U1A has been implicated in alternative splicing regulation, RNA export, and the maintenance of genomic stability. Phosphorylation of U1A by casein kinase 2 modulates its RNA‑binding affinity and may influence splice site selection.

Clinically, mutations or dysregulation of SNRPA have been associated with certain neurodegenerative disorders and cancers, where aberrant splicing patterns are observed. U1A also serves as a model system in structural biology; high‑resolution crystal structures of its RRMs have provided insights into RNA‑protein recognition mechanisms that are applicable to many other RNA‑binding proteins.