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

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.

Automated summary

Long non-coding RNAs (lncRNAs) play a key role in regulating cellular senescence. One particular lncRNA associated with senescence, Senescence Associated Long Non-coding RNA (SALNR), has been found to be down-regulated in various cellular models of senescence. However, our investigation reveals that SALNR may not exist as an independent transcript, but rather as a predicted isoform of the HELLS gene. This finding highlights the importance of HELLS in the senescence and aging process.