Linking a nuclear lncRNA to cytoplasmic lysosome integrity and cell death

Long non-coding RNAs (ncRNAs) are non-coding RNAs that are 200 nucleotides or greater in length and can function in a variety of biological processes (1). Although the human genome can encode up to approximately 100,000 lncRNAs, most lncRNAs are in low abundance and it is difficult to determine their actual function. However, a subset of highly expressed lncRNAs are regulatory RNAs with profound functions in regulating gene transcription, paratach formation, RNA splicing, messenger RNA (mRNA) stability ) and protein degradation (13). Most lncRNAs are transcribed by RNA polymerase II and their expression is regulated both at the level of transcription and RNA processing (1) and by various viral infections (4, 5). In PNAS, Yang et al. (6) explore the expression profile of cellular lncRNAs in the presence of the histone deacetylase inhibitor Trichostatin A and identify an approximately 2 kb long nuclear lncRNA, ENSG00000273148 or LINC00653, highly expressed from chr20 in lung cancer non-small cell p53-null cells of the NCI-H1299 cell line. Yang et al. (6) show that it regulates the expression of lysosomal-associated transmembrane protein 5 (LAPTM5) and lysosome cell death (LCD); the authors thus name this lncRNA an LCD regulator, or LCDR.

Lysosomes are small membrane-bound cytoplasmic and acidic organelles and contain more than 50 hydrolytic enzymes (seven) for the digestion of various extra- and intracellular materials to maintain cellular homeostasis and destroy invading pathogens. Among ∼25 integral lysosomal membrane proteins (8), LAPTM5, which was thought to be specifically expressed in hematopoietic cells (9) to maintain the integrity of the lysosome membrane (8), is also highly expressed in human bladder cancer tissue. Knockdown (KD) of LAPTM5 expression in T24 and 5637 bladder cancer cell lines inhibits cell proliferation and colony formation (ten), but the mechanism of LAPTM5 in relation to the cell…


1To whom correspondence may be addressed. E-mail: zhengt{at}exchange.nih.gov.

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