PMID- 33588838
OWN - NLM
STAT- MEDLINE
DCOM- 20211001
LR  - 20231109
IS  - 1741-7007 (Electronic)
IS  - 1741-7007 (Linking)
VI  - 19
IP  - 1
DP  - 2021 Feb 15
TI  - Characterizing RNA stability genome-wide through combined analysis of PRO-seq and 
      RNA-seq data.
PG  - 30
LID - 10.1186/s12915-021-00949-x [doi]
LID - 30
AB  - BACKGROUND: The concentrations of distinct types of RNA in cells result from a 
      dynamic equilibrium between RNA synthesis and decay. Despite the critical 
      importance of RNA decay rates, current approaches for measuring them are 
      generally labor-intensive, limited in sensitivity, and/or disruptive to normal 
      cellular processes. Here, we introduce a simple method for estimating relative 
      RNA half-lives that is based on two standard and widely available high-throughput 
      assays: Precision Run-On sequencing (PRO-seq) and RNA sequencing (RNA-seq). 
      RESULTS: Our method treats PRO-seq as a measure of transcription rate and RNA-seq 
      as a measure of RNA concentration, and estimates the rate of RNA decay required 
      for a steady-state equilibrium. We show that this approach can be used to assay 
      relative RNA half-lives genome-wide, with good accuracy and sensitivity for both 
      coding and noncoding transcription units. Using a structural equation model 
      (SEM), we test several features of transcription units, nearby DNA sequences, and 
      nearby epigenomic marks for associations with RNA stability after controlling for 
      their effects on transcription. We find that RNA splicing-related features are 
      positively correlated with RNA stability, whereas features related to miRNA 
      binding and DNA methylation are negatively correlated with RNA stability. 
      Furthermore, we find that a measure based on U1 binding and polyadenylation sites 
      distinguishes between unstable noncoding and stable coding transcripts but is not 
      predictive of relative stability within the mRNA or lincRNA classes. We also 
      identify several histone modifications that are associated with RNA stability. 
      CONCLUSION: We introduce an approach for estimating the relative half-lives of 
      individual RNAs. Together, our estimation method and systematic analysis shed 
      light on the pervasive impacts of RNA stability on cellular RNA concentrations.
FAU - Blumberg, Amit
AU  - Blumberg A
AD  - Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold 
      Spring Harbor, NY, USA.
FAU - Zhao, Yixin
AU  - Zhao Y
AD  - Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold 
      Spring Harbor, NY, USA.
FAU - Huang, Yi-Fei
AU  - Huang YF
AD  - Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold 
      Spring Harbor, NY, USA.
AD  - Present Address: Department of Biology and Huck Institutes of the Life Sciences, 
      Pennsylvania State University, University Park, PA, USA.
FAU - Dukler, Noah
AU  - Dukler N
AD  - Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold 
      Spring Harbor, NY, USA.
FAU - Rice, Edward J
AU  - Rice EJ
AD  - Baker Institute for Animal Health, College of Veterinary Medicine, Cornell 
      University, Ithaca, NY, USA.
FAU - Chivu, Alexandra G
AU  - Chivu AG
AD  - Baker Institute for Animal Health, College of Veterinary Medicine, Cornell 
      University, Ithaca, NY, USA.
FAU - Krumholz, Katie
AU  - Krumholz K
AD  - Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold 
      Spring Harbor, NY, USA.
FAU - Danko, Charles G
AU  - Danko CG
AD  - Baker Institute for Animal Health, College of Veterinary Medicine, Cornell 
      University, Ithaca, NY, USA.
FAU - Siepel, Adam
AU  - Siepel A
AUID- ORCID: 0000-0002-3557-7219
AD  - Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold 
      Spring Harbor, NY, USA. asiepel@cshl.edu.
LA  - eng
GR  - R01 HG010346/HG/NHGRI NIH HHS/United States
GR  - R35-GM127070/NH/NIH HHS/United States
GR  - R01-HG009309/NH/NIH HHS/United States
GR  - R35 GM127070/GM/NIGMS NIH HHS/United States
GR  - R01 HG009309/HG/NHGRI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210215
PL  - England
TA  - BMC Biol
JT  - BMC biology
JID - 101190720
SB  - IM
MH  - *Genomic Instability
MH  - High-Throughput Nucleotide Sequencing/instrumentation/*methods
MH  - Humans
MH  - *RNA Stability
MH  - RNA-Seq/methods
PMC - PMC7885420
OTO - NOTNLM
OT  - Epigenomics
OT  - PRO-seq
OT  - RNA half-life
OT  - RNA splicing
OT  - Structural equation modeling
COIS- The authors declare that they have no competing interests.
EDAT- 2021/02/17 06:00
MHDA- 2021/10/02 06:00
PMCR- 2021/02/15
CRDT- 2021/02/16 05:43
PHST- 2020/11/24 00:00 [received]
PHST- 2021/01/05 00:00 [accepted]
PHST- 2021/02/16 05:43 [entrez]
PHST- 2021/02/17 06:00 [pubmed]
PHST- 2021/10/02 06:00 [medline]
PHST- 2021/02/15 00:00 [pmc-release]
AID - 10.1186/s12915-021-00949-x [pii]
AID - 949 [pii]
AID - 10.1186/s12915-021-00949-x [doi]
PST - epublish
SO  - BMC Biol. 2021 Feb 15;19(1):30. doi: 10.1186/s12915-021-00949-x.