Evolutionary conservation of RNA sequence and structure.
RNA folding
conserved RNA structure
covariation
Journal
Wiley interdisciplinary reviews. RNA
ISSN: 1757-7012
Titre abrégé: Wiley Interdiscip Rev RNA
Pays: United States
ID NLM: 101536955
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
24
02
2021
received:
17
12
2020
accepted:
25
02
2021
pubmed:
24
3
2021
medline:
15
12
2021
entrez:
23
3
2021
Statut:
ppublish
Résumé
An RNA structure prediction from a single-sequence RNA folding program is not evidence for an RNA whose structure is important for function. Random sequences have plausible and complex predicted structures not easily distinguishable from those of structural RNAs. How to tell when an RNA has a conserved structure is a question that requires looking at the evolutionary signature left by the conserved RNA. This question is important not just for long noncoding RNAs which usually lack an identified function, but also for RNA binding protein motifs which can be single stranded RNAs or structures. Here we review recent advances using sequence and structural analysis to determine when RNA structure is conserved or not. Although covariation measures assess structural RNA conservation, one must distinguish covariation due to RNA structure from covariation due to independent phylogenetic substitutions. We review a statistical test to measure false positives expected under the null hypothesis of phylogenetic covariation alone (specificity). We also review a complementary test that measures power, that is, expected covariation derived from sequence variation alone (sensitivity). Power in the absence of covariation signals the absence of a conserved RNA structure. We analyze artifacts that falsely identify conserved RNA structure such as the misuse of programs that do not assess significance, the use of inappropriate statistics confounded by signals other than covariation, or misalignments that induce spurious covariation. Among artifacts that obscure the signal of a conserved RNA structure, we discuss the inclusion of pseudogenes in alignments which increase power but destroy covariation. This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA Evolution and Genomics > Computational Analyses of RNA RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution.
Identifiants
pubmed: 33754485
doi: 10.1002/wrna.1649
pmc: PMC8250186
doi:
Substances chimiques
RNA, Long Noncoding
0
RNA
63231-63-0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1649Informations de copyright
© 2021 The Author. WIREs RNA published by Wiley Periodicals LLC.
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