U-rich elements drive pervasive cryptic splicing in 3' UTR massively parallel reporter assays.

ABSTRACT: Non-coding RNA sequences play essential roles in orchestrating gene expression. However, the sequence codes and mechanisms underpinning post-transcriptional regulation remain incompletely understood. Here, we revisit the finding from a prior massively parallel reporter assay (MPRA) that AU-rich (U-rich) elements in 3' untranslated regions (3' UTRs) can drive upregulation or downregulation of mRNA expression depending on 3' UTR context. We unexpectedly discover that this variable regulation arises from widespread cryptic splicing, predominately from an unannotated splice donor in the coding sequence of GFP to diverse acceptor sites in reporter 3' UTRs. Splicing is activated by U-rich sequences, which function as potent position-dependent regulators of 5' and 3' splice site choice and overal

SUBMITTER: Dao K 

PROVIDER: S-EPMC11326173 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature