作者: Yuri Vyatkin , Philipp Kapranov , Denis Antonets , Maxim Ri , Yao Qi
DOI: 10.1186/S12915-021-01044-X
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摘要: Background The majority of the human genome is transcribed in form long non-coding (lnc) RNAs. While these transcripts have attracted considerable interest, their molecular mechanisms function and biological significance remain controversial. One main reasons behind this lies significant challenges posed by lncRNAs requiring development novel methods concepts to unravel functionality. Existing often lack cross-validation independent confirmation different methodologies therefore leave ambiguity as authenticity outcomes. Nonetheless, despite all caveats, it appears that may function, at least part, regulating other genes via chromatin interactions. Therefore, a lncRNA could be inferred from regulates. In work, we present genome-wide functional annotation strategy for based on identification regulatory networks integration three distinct types approaches: co-expression analysis, mapping lncRNA-chromatin interactions, assaying effects knockdowns obtained using an inducible highly specific CRISPR/Cas13 system. Results We applied annotate 407 very intergenic (vlinc) RNAs belonging widespread subclass lncRNAs. show vlincRNAs indeed appear regulate multiple encoding proteins predominantly involved RNA- development-related functions, cell cycle, cellular adhesion mechanism involving proximity between targets nucleus. A typical can both positive negative regulator trans cis. Finally, potentially represent components DNA damage response are functionally important ability cancer cells survive genotoxic stress. Conclusions This study provides strong evidence role vlincRNA class played hidden layer RNA-based regulation complex systems.