title: Senescence-associated lncRNAs: senescence-associated long noncoding RNAs.
abstract: Noncoding RNAs include small transcripts, such as microRNAs and piwi-interacting RNAs, and a wide range of long noncoding RNAs (lncRNAs). Although many lncRNAs have been identified, only a small number of lncRNAs have been characterized functionally. Here, we sought to identify lncRNAs differentially expressed during replicative senescence. We compared lncRNAs expressed in proliferating, early-passage, 'young' human diploid WI-38 fibroblasts [population doubling (PDL) 20] with those expressed in senescent, late-passage, 'old' fibroblasts (PDL 52) by RNA sequencing (RNA-Seq). Numerous transcripts in all lncRNA groups (antisense lncRNAs, pseudogene-encoded lncRNAs, previously described lncRNAs and novel lncRNAs) were validated using reverse transcription (RT) and real-time, quantitative (q)PCR. Among the novel senescence-associated lncRNAs (SAL-RNAs) showing lower abundance in senescent cells, SAL-RNA1 (XLOC_023166) was found to delay senescence, because reducing SAL-RNA1 levels enhanced the appearance of phenotypic traits of senescence, including an enlarged morphology, positive β-galactosidase activity, and heightened p53 levels. Our results reveal that the expression of known and novel lncRNAs changes with senescence and suggests that SAL-RNAs play direct regulatory roles in this important cellular process.
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
authors.forename: Kotb
authors.initials: K
authors.lastname: Abdelmohsen
authors.forename: Amaresh
authors.initials: A
authors.lastname: Panda
authors.forename: Min-Ju
authors.initials: MJ
authors.lastname: Kang
authors.forename: Jason
authors.initials: J
authors.lastname: Xu
authors.forename: Roza
authors.initials: R
authors.lastname: Selimyan
authors.forename: Je-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martindale
authors.forename: Supriyo
authors.initials: S
authors.lastname: De
authors.forename: William H
authors.initials: WH
authors.lastname: Wood
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
mesh_terms: D000375:Aging / Q000235:genetics*; D048708:Cell Growth Processes / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D011544:Pseudogenes; D016372:RNA, Antisense / Q000096:biosynthesis / Q000235:genetics; D062085:RNA, Long Noncoding / Q000096:biosynthesis / Q000235:genetics*; D059467:Transcriptome; D014162:Transfection
chemical_list: D016372:RNA, Antisense; D062085:RNA, Long Noncoding
keywords: noncoding; post-transcriptional gene regulation; proliferation; senescence-associated gene expression patterns; transcriptome