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Publication : Alternative transcribed 3' isoform of long non-coding RNA Malat1 inhibits mouse retinal oxidative stress.

First Author  Ghanam AR Year  2023
Journal  iScience Volume  26
Issue  1 Pages  105740
PubMed ID  36594014 Mgi Jnum  J:352042
Mgi Id  MGI:7424360 Doi  10.1016/j.isci.2022.105740
Citation  Ghanam AR, et al. (2023) Alternative transcribed 3' isoform of long non-coding RNA Malat1 inhibits mouse retinal oxidative stress. iScience 26(1):105740
abstractText  The function of the cancer-associated lncRNA Malat1 during aging is as-of-yet uncharacterized. Here, we show that Malat1 interacts with Nucleophosmin (NPM) in young mouse brain, and with Lamin A/C, hnRNP C, and KAP1 with age. RNA-seq and RT-qPCR reveal a persistent expression of Malat1_2 (the 3'isoform of Malat1) in Malat1Delta1 (5'-1.5 kb deletion) mouse retinas and brains at 1/4(th) level of the full-length Malat1, while Malat1_1 (the 5'isoform) in Malat1Delta2 (deletion of 3'-conserved 5.7 kb) at a much lower level, suggesting an internal promoter driving the 3' isoform. The 1774 and 496 differentially expressed genes in Malat1Delta2 and Malat1Delta1 brains, respectively, suggest the 3' isoform regulates gene expression in trans and the 5' isoform in cis. Consistently, Malat1Delta2 mice show increased age-dependent retinal oxidative stress and corneal opacity, while Malat1Delta1 mice show no obvious phenotype. Collectively, this study reveals a physiological function of the lncRNA Malat1 3'-isoform during the aging process.
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