Distinct and redundant roles of nuclear RNA exosome targeting complexes

ABSTRACT: Degradation of transcripts in mammalian nuclei is primarily facilitated by the RNA exosome. To obtain substrate specificity, the exosome is aided by adaptors; in the nucleoplasm, the Nuclear EXosome Targeting (NEXT) complex and the PolyA (pA) eXsome Targeting (PAXT) connection. However, how exact targeting is achieved remains enigmatic. Employing high-resolution 3’end sequencing of both steady state and newly produced pA+ and pA- RNA, we demonstrate that NEXT substrates arise from heterogenous and predominantly pA- 3’ends often covering kb-wide genomic regions. In contrast, PAXT targets harbor well-defined pA+ 3’ends defined by canonical pA site usage. Irrespective this clear division, NEXT and PAXT act redundantly in two ways: i) Regional redundancy: The majority of exosome-targeted transcription units produce both NEXT- and PAXT-sensitive RNA isoforms; and ii) Isoform redundancy: The PAXT connection ensures the fail-safe decay of post-transcriptionally polyadenylated NEXT targets. In conjunction, this provides for the efficient nuclear removal of superfluous RNA.

ORGANISM(S): Homo sapiens

PROVIDER: GSE137612 | GEO | 2020/02/06

REPOSITORIES: GEO