title: Long non-coding RNA gadd7 interacts with TDP-43 and regulates Cdk6 mRNA decay.
abstract: Long non-coding RNAs (lncRNAs) transcribed extensively from the genome have been proposed to be key regulators of diverse biological processes. However, little is known about the role of lncRNAs in regulation of the cell-cycle G1/S checkpoint following DNA damage, a key step in the maintenance of genomic fidelity. Here we show that growth-arrested DNA damage-inducible gene 7 (gadd7), a DNA damage-inducible lncRNA, regulates the G1/S checkpoint in response to UV irradiation. Interestingly, UV-induced gadd7 directly binds to TAR DNA-binding protein (TDP-43) and interferes with the interaction between TDP-43 and cyclin-dependent kinase 6 (Cdk6) mRNA, resulting in Cdk6 mRNA degradation. These findings demonstrate a role for gadd7 in controlling cell-cycle progression and define a novel mechanism by which lncRNAs modulate mRNA expression at the post-transcriptional level by altering mRNA stability.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Weimin
authors.initials: W
authors.lastname: Zhang
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
mesh_terms: D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle; D006224:Cricetinae; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D020871:RNA Stability / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014466:Ultraviolet Rays
chemical_list: D004268:DNA-Binding Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D051361:Cyclin-Dependent Kinase 6