snRNA

Small nuclear RNA (snRNA) refers to a class of small non-coding RNA molecules that, together with proteins, form the core components of the spliceosome, the complex that removes introns from pre-mRNA in eukaryotes. The majority belong to the U family, including U1, U2, U4, U5, and U6. A minor set exists for the alternative or “minor” spliceosome, including U11, U12, U4atac, U5, and U6atac. snRNAs are relatively short and are highly conserved across eukaryotic species, reflecting their essential role in RNA processing.

Biogenesis and maturation: Most snRNA genes are transcribed by RNA polymerase II (U1, U2, U4, U5) or by RNA polymerase III (U6 and related snRNAs). After transcription, snRNAs undergo 5' capping and 3' end processing and are assembled with specific proteins to form small nuclear ribonucleoproteins (snRNPs). For the major snRNPs, Sm core proteins assemble onto a conserved Sm site in the cytoplasm, after which the snRNPs are imported back into the nucleus. U6 follows a distinct maturation pathway and associates with different proteins, such as LSm. In the nucleus, snRNPs accumulate in subnuclear structures like Cajal bodies, where final assembly and recycling occur.

Function in splicing: In the major spliceosome, U1 recognizes the 5' splice site, U2 binds the branch point, and U4/U6 together with U5 participate in forming the catalytic core. The snRNPs undergo dynamic rearrangements to activate the spliceosome and catalyze two transesterification reactions that remove introns and join exons. The minor spliceosome uses the U11/U12 complex with U5, U6atac, and U4atac to process a subset of introns.

Clinical and evolutionary notes: snRNA genes and the snRNP biogenesis pathway are evolutionarily conserved. Defects in snRNP components or snRNA maturation can disrupt splicing and are linked, in various contexts, to human diseases, including neurodegenerative disorders.