The Human Nuclear Exosome Targeting Complex Is Loaded onto Newly Synthesized RNA to Direct Early Ribonucleolysis

TY - JOUR

T1 - The Human Nuclear Exosome Targeting Complex Is Loaded onto Newly Synthesized RNA to Direct Early Ribonucleolysis

AU - Lubas, Michal Szymon

AU - Andersen, Peter Refsing

AU - Schein, Aleks

AU - Dziembowski, Andrzej

AU - Kudla, Grzegorz

AU - Jensen, Torben Heick

N1 - Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2015/1/13

Y1 - 2015/1/13

N2 - The RNA exosome complex constitutes the major nuclear eukaryotic 3'-5' exonuclease. Outside of nucleoli, the human nucleoplasmic exosome is directed to some of its substrates by the nuclear exosome targeting (NEXT) complex. How NEXT targets RNA has remained elusive. Using an in vivo crosslinking approach, we report global RNA binding sites of RBM7, a key component of NEXT. RBM7 associates broadly with RNA polymerase II-derived RNA, including pre-mRNA and short-lived exosome substrates such as promoter upstream transcripts (PROMPTs), enhancer RNAs (eRNAs), and 3'-extended products from snRNA and replication-dependent histone genes. Within pre-mRNA, RBM7 accumulates at the 3' ends of introns, and pulse-labeling experiments demonstrate that RBM7/NEXT defines an early exosome-targeting pathway for 3'-extended snoRNAs derived from such introns. We propose that RBM7 is generally loaded onto newly synthesized RNA to accommodate exosome action in case of available unprotected RNA 3' ends.

AB - The RNA exosome complex constitutes the major nuclear eukaryotic 3'-5' exonuclease. Outside of nucleoli, the human nucleoplasmic exosome is directed to some of its substrates by the nuclear exosome targeting (NEXT) complex. How NEXT targets RNA has remained elusive. Using an in vivo crosslinking approach, we report global RNA binding sites of RBM7, a key component of NEXT. RBM7 associates broadly with RNA polymerase II-derived RNA, including pre-mRNA and short-lived exosome substrates such as promoter upstream transcripts (PROMPTs), enhancer RNAs (eRNAs), and 3'-extended products from snRNA and replication-dependent histone genes. Within pre-mRNA, RBM7 accumulates at the 3' ends of introns, and pulse-labeling experiments demonstrate that RBM7/NEXT defines an early exosome-targeting pathway for 3'-extended snoRNAs derived from such introns. We propose that RBM7 is generally loaded onto newly synthesized RNA to accommodate exosome action in case of available unprotected RNA 3' ends.

U2 - 10.1016/j.celrep.2014.12.026

DO - 10.1016/j.celrep.2014.12.026

M3 - Journal article

C2 - 25578728

SN - 2211-1247

VL - 10

SP - 178

EP - 183

JO - Cell Reports

JF - Cell Reports

IS - 2

ER -