An Unanticipated Modulation of Cyclin-Dependent Kinase Inhibitors: The Role of Long Non-Coding RNAs

Cells. 2022 Apr 14;11(8):1346. doi: 10.3390/cells11081346.

Abstract

It is now definitively established that a large part of the human genome is transcribed. However, only a scarce percentage of the transcriptome (about 1.2%) consists of RNAs that are translated into proteins, while the large majority of transcripts include a variety of RNA families with different dimensions and functions. Within this heterogeneous RNA world, a significant fraction consists of sequences with a length of more than 200 bases that form the so-called long non-coding RNA family. The functions of long non-coding RNAs range from the regulation of gene transcription to the changes in DNA topology and nucleosome modification and structural organization, to paraspeckle formation and cellular organelles maturation. This review is focused on the role of long non-coding RNAs as regulators of cyclin-dependent kinase inhibitors' (CDKIs) levels and activities. Cyclin-dependent kinases are enzymes necessary for the tuned progression of the cell division cycle. The control of their activity takes place at various levels. Among these, interaction with CDKIs is a vital mechanism. Through CDKI modulation, long non-coding RNAs implement control over cellular physiology and are associated with numerous pathologies. However, although there are robust data in the literature, the role of long non-coding RNAs in the modulation of CDKIs appears to still be underestimated, as well as their importance in cell proliferation control.

Keywords: ANRIL; CDK inhibitors; long non-coding RNAs; p15INK4B Cip/Kip CDK inhibitors; p16INK4A; p21Cip1; p27Kip1; p57Kip2.

Publication types

  • Review

MeSH terms

  • Cyclin-Dependent Kinase Inhibitor Proteins*
  • Cyclin-Dependent Kinases / metabolism
  • Humans
  • RNA, Long Noncoding* / genetics

Substances

  • Cyclin-Dependent Kinase Inhibitor Proteins
  • RNA, Long Noncoding
  • Cyclin-Dependent Kinases