Lost in HELLS: Disentangling the mystery of SALNR existence in senescence cellular models

PLoS One. 2023 May 30;18(5):e0286104. doi: 10.1371/journal.pone.0286104. eCollection 2023.

Abstract

Long non-coding RNAs (lncRNAs) have emerged as key regulators of cellular senescence by transcriptionally and post-transcriptionally modulating the expression of many important genes involved in senescence-associated pathways and processes. Among the different lncRNAs associated to senescence, Senescence Associated Long Non-coding RNA (SALNR) was found to be down-regulated in different cellular models of senescence. Since its release in 2015, SALNR has not been annotated in any database or public repository, and no other experimental data have been published. The SALNR sequence is located on the long arm of chromosome 10, at band 10q23.33, and it overlaps the 3' end of the HELLS gene. This investigation helped to unravel the mystery of the existence of SALNR by analyzing publicly available short- and long-read RNA sequencing data sets and RT-PCR analysis in human tissues and cell lines. Additionally, the expression of HELLS has been studied in cellular models of replicative senescence, both in silico and in vitro. Our findings, while not supporting the actual existence of SALNR as an independent transcript in the analyzed experimental models, demonstrate the expression of a predicted HELLS isoform entirely covering the SALNR genomic region. Furthermore, we observed a strong down-regulation of HELLS in senescent cells versus proliferating cells, supporting its role in the senescence and aging process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cellular Senescence / genetics
  • DNA Helicases / genetics
  • Down-Regulation
  • Fibroblasts / physiology
  • Humans
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding
  • HELLS protein, human
  • DNA Helicases

Grants and funding

This work was supported by ‘Piano di sostegno alla Ricerca 2020’ Grant (Università degli Studi di Milano, award no. PSR2020_BATTAGLIA_LINEA_B to CB and MV; award no. PSR2020_CATTANEO_LINEA_C to MGC), ‘NutrAge’ Grant (CNR-FOE 2021, award no. DBA.AD005.225) to AC. Bioinformatics analysis has been executed on ICT infrastructure funded by CNR-BiOmics project (Italian MUR, PON R&I 2014-2020 D.D. n. 424 28/02/2018) to FL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.