A link between nuclear RNA surveillance, the human exosome and RNA polymerase II transcriptional termination.
In eukaryotes, the production of mature messenger RNA that exits the nucleus to be translated into protein in the cytoplasm requires precise and extensive modification of the nascent transcript. Any failure that compromises the integrity of an mRNA may cause its retention in the nucleus and trigger its degradation. Multiple studies indicate that mRNAs with processing defects accumulate in nuclear foci or 'dots' located near the site of transcription, but how exactly are defective RNAs recognized and tethered is still unknown. Here, we present evidence suggesting that unprocessed β-globin transcripts render RNA polymerase II (Pol II) incompetent for termination and that this quality control process requires the integrity of the nuclear exosome. Our results show that unprocessed pre-mRNAs remain tethered to the DNA template in association with Pol II, in an Rrp6-dependent manner. This reveals an unprecedented link between nuclear RNA surveillance, the exosome and Pol II transcriptional termination.
de Almeida
Sérgio F
SF
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
García-Sacristán
Ana
A
Custódio
Noélia
N
Carmo-Fonseca
Maria
M
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D005095:Exoribonucleases / Q000502:physiology*; D063326:Exosome Multienzyme Ribonuclease Complex; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology*; D021122:Protein Subunits; D012319:RNA Polymerase II / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D013698:Templates, Genetic; D014158:Transcription, Genetic; D055544:beta-Globins / Q000235:genetics
D009687:Nuclear Proteins; D021122:Protein Subunits; D012322:RNA Precursors; D012333:RNA, Messenger; D055544:beta-Globins; D012319:RNA Polymerase II; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C077044:EXOSC10 protein, human