RNA timestamps identify the age of single molecules in RNA sequencing.
Journal
Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
18
02
2020
accepted:
07
09
2020
revised:
27
08
2020
pubmed:
21
10
2020
medline:
15
4
2021
entrez:
20
10
2020
Statut:
ppublish
Résumé
Current approaches to single-cell RNA sequencing (RNA-seq) provide only limited information about the dynamics of gene expression. Here we present RNA timestamps, a method for inferring the age of individual RNAs in RNA-seq data by exploiting RNA editing. To introduce timestamps, we tag RNA with a reporter motif consisting of multiple MS2 binding sites that recruit the adenosine deaminase ADAR2 fused to an MS2 capsid protein. ADAR2 binding to tagged RNA causes A-to-I edits to accumulate over time, allowing the age of the RNA to be inferred with hour-scale accuracy. By combining observations of multiple timestamped RNAs driven by the same promoter, we can determine when the promoter was active. We demonstrate that the system can infer the presence and timing of multiple past transcriptional events. Finally, we apply the method to cluster single cells according to the timing of past transcriptional activity. RNA timestamps will allow the incorporation of temporal information into RNA-seq workflows.
Identifiants
pubmed: 33077959
doi: 10.1038/s41587-020-0704-z
pii: 10.1038/s41587-020-0704-z
pmc: PMC7956158
mid: NIHMS1647079
doi:
Substances chimiques
RNA-Binding Proteins
0
RNA
63231-63-0
ADARB1 protein, human
EC 3.5.4.4
Adenosine Deaminase
EC 3.5.4.4
Types de publication
Letter
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
320-325Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM087237
Pays : United States
Organisme : NINDS NIH HHS
ID : UF1 NS107697
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008313
Pays : United States
Organisme : NIH HHS
ID : DP5 OD024583
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA029639
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH114031
Pays : United States
Organisme : NHGRI NIH HHS
ID : RM1 HG008525
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH103910
Pays : United States
Organisme : NINDS NIH HHS
ID : DP1 NS087724
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Commentaires et corrections
Type : CommentIn
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