U1 snRNP-mediated poly(A) site suppression

Abstract

The spliceosomal component U1snRNP commits pre-mRNAs to the splicing pathway. Recently, a nuclear RNA surveillance function has been ascribed to U1, namely the suppression of intronic polyadenylation sites. This surveillance holds regulatory potential as it alters the 3' ends of certain recep-tor tyrosine kinase mRNAs. However, suppression of 3' end processing by U1 snRNP is also the cause of a severe genetic disorder. We described a 3'UTR point mutation creating a 5'SS leading to U1-mediated suppression of 3' end for-mation. Thus, the inhibitory function of U1 is both beneficial and deleterious where misled. The exact mechanism of how U1 interferes with 3' end process-ing remains unclear. According to our data, U1 snRNP already interferes with cleavage or poly(A) site selection instead of directly inhibiting poly(A) polymerase as previously assumed. Here, we pres-ent alternative models for U1-mediated poly(A) site suppression and discuss the implications for RNA quality control and disease-related mutations.