Biogenic mechanisms and utilization of small RNAs derived from human protein-coding genes

TY - JOUR

T1 - Biogenic mechanisms and utilization of small RNAs derived from human protein-coding genes

AU - Valen, Eivind

AU - Preker, Pascal

AU - Andersen, Peter Refsing

AU - Zhao, Xiaobei

AU - Chen, Yun

AU - Ender, Christine

AU - Dueck, Anne

AU - Meister, Gunter

AU - Sandelin, Albin Gustav

AU - Jensen, Torben Heick

PY - 2011/9

Y1 - 2011/9

N2 - Efforts to catalog eukaryotic transcripts have uncovered many small RNAs (sRNAs) derived from gene termini and splice sites. Their biogenesis pathways are largely unknown, but a mechanism based on backtracking of RNA polymerase II (RNAPII) has been suggested. By sequencing transcripts 12-100 nucleotides in length from cells depleted of major RNA degradation enzymes and RNAs associated with Argonaute (AGO1/2) effector proteins, we provide mechanistic models for sRNA production. We suggest that neither splice site-associated (SSa) nor transcription start site-associated (TSSa) RNAs arise from RNAPII backtracking. Instead, SSa RNAs are largely degradation products of splicing intermediates, whereas TSSa RNAs probably derive from nascent RNAs protected by stalled RNAPII against nucleolysis. We also reveal new AGO1/2-associated RNAs derived from 3-2 ends of introns and from mRNA 3-2 UTRs that appear to draw from noncanonical microRNA biogenesis pathways.

AB - Efforts to catalog eukaryotic transcripts have uncovered many small RNAs (sRNAs) derived from gene termini and splice sites. Their biogenesis pathways are largely unknown, but a mechanism based on backtracking of RNA polymerase II (RNAPII) has been suggested. By sequencing transcripts 12-100 nucleotides in length from cells depleted of major RNA degradation enzymes and RNAs associated with Argonaute (AGO1/2) effector proteins, we provide mechanistic models for sRNA production. We suggest that neither splice site-associated (SSa) nor transcription start site-associated (TSSa) RNAs arise from RNAPII backtracking. Instead, SSa RNAs are largely degradation products of splicing intermediates, whereas TSSa RNAs probably derive from nascent RNAs protected by stalled RNAPII against nucleolysis. We also reveal new AGO1/2-associated RNAs derived from 3-2 ends of introns and from mRNA 3-2 UTRs that appear to draw from noncanonical microRNA biogenesis pathways.

U2 - 10.1038/nsmb.2091

DO - 10.1038/nsmb.2091

M3 - Journal article

C2 - 21822281

SN - 1545-9993

VL - 18

SP - 1075

EP - 1082

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 9

ER -