Single nucleotide polymorphisms affect RNA-protein interactions at a distance through modulation of RNA secondary structures.
Journal
PLoS computational biology
ISSN: 1553-7358
Titre abrégé: PLoS Comput Biol
Pays: United States
ID NLM: 101238922
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
23
10
2019
accepted:
06
04
2020
revised:
19
05
2020
pubmed:
8
5
2020
medline:
29
8
2020
entrez:
8
5
2020
Statut:
epublish
Résumé
Single nucleotide polymorphisms are widely associated with disease, but the ways in which they cause altered phenotypes are often unclear, especially when they appear in non-coding regions. One way in which non-coding polymorphisms could cause disease is by affecting crucial RNA-protein interactions. While it is clear that changing a protein binding motif will alter protein binding, it has been shown that single nucleotide polymorphisms can affect RNA secondary structure, and here we show that single nucleotide polymorphisms can affect RNA-protein interactions from outside binding motifs through altered RNA secondary structure. By using a modified version of the Vienna Package and PAR-CLIP data for HuR (ELAVL1) in humans we characterize the genome-wide effect of single nucleotide polymorphisms on HuR binding and show that they can have a many-fold effect on the affinity of HuR binding to RNA transcripts from tens of bases away. We also find some evidence that the effect of single nucleotide polymorphisms on protein binding might be under selection, with the non-reference alleles tending to make it harder for a protein to bind.
Identifiants
pubmed: 32379750
doi: 10.1371/journal.pcbi.1007852
pii: PCOMPBIOL-D-19-01860
pmc: PMC7237046
doi:
Substances chimiques
RNA, Messenger
0
RNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007852Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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