Genome-Wide Analysis of Human Long Noncoding RNAs: A Provocative Review

Chris P. Ponting, Wilfried Haerty

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)

Abstract

Do long noncoding RNAs (lncRNAs) contribute little or substantively to human biology? To address how lncRNA loci and their transcripts, structures, interactions, and functions contribute to human traits and disease, we adopt a genome-wide perspective. We intend to provoke alternative interpretation of questionable evidence and thorough inquiry into unsubstantiated claims. We discuss pitfalls of lncRNA experimental and computational methods as well as opposing interpretations of their results. The majority of evidence, we argue, indicates that most lncRNA transcript models reflect transcriptional noise or provide minor regulatory roles, leaving relatively few human lncRNAs that contribute centrally to human development, physiology, or behavior. These important few tend to be spliced and better conserved but lack a simple syntax relating sequence to structure and mechanism, and so resist simple categorization. This genome-wide view should help investigators prioritize individual lncRNAs based on their likely contribution to human biology.

Original languageEnglish
Pages (from-to)153-172
Number of pages20
JournalAnnual Review of Genomics and Human Genetics
Volume23
Early online date8 Apr 2022
DOIs
Publication statusPublished - 31 Aug 2022

Keywords

  • evolutionary constraint
  • knockout phenotype
  • molecular mechanism
  • RNA structure
  • subcellular localization
  • transcriptional noise

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