Accumulation of Mitochondrial RPPH1 RNA Is Associated with Cellular Senescence

Abstract

Post-transcriptional gene regulation is an important step in the regulation of eukaryotic gene expression. Subcellular compartmentalization of RNA species plays a crucial role in the control of mRNA turnover, spatial restriction of protein synthesis, and the formation of macromolecular complexes. Although long noncoding RNAs (lncRNAs) are one of the key regulators of post-transcriptional gene expression, it is not heavily studied whether localization of lncRNAs in subcellular organelles has functional consequences. Here, we report on mitochondrial lncRNAs whose expression fluctuates in the process of cellular senescence. One of the mitochondrial lncRNAs, RPPH1 RNA, is overexpressed and accumulates in mitochondria of senescent fibroblasts, possibly modulated by the RNA-binding protein AUF1. In addition, RPPH1 RNA overexpression promotes spontaneous replicative cellular senescence in proliferating fibroblasts. Using MS2 aptamer-based RNA affinity purification strategy, we identified putative target mRNAs of RPPH1 RNA and revealed that partial complementarity of RPPH1 RNA to its target mRNAs prevents those mRNAs decay in proliferating fibroblasts. Altogether, our results demonstrate the role of mitochondrial noncoding RNA in the regulation of mRNA stability and cellular senescence.

Zrsr2 and functional U12-dependent spliceosome are necessary for follicular development

“…Moreover, up-regulation of genes that are related to the immune system and inflammatory processes in the granulosa cells could indicate the presence of a defense mechanism to prevent the oocytes with an aberrant expression pattern from further developing. Also, the highest up-regulation of the IR events is observed in the GC-AG U2-type intron of Rpph1 , a lncRNA that is part of the ribonucleoprotein RNAse P, involved in the cellular translation system, in rRNA and mRNA cleavage, as well as mRNA stability, senescence, inflammation, and chromatin remodeling ( Jarrous, 2017 ; Lee et al., 2021 ). Up-regulation of Rpph1 has been related to breast and colorectal cancer ( Liang et al., 2019 ); furthermore, it has been suggested that RPPH1 could enhance human acute myeloid leukemia cell proliferation, migration, and invasion ( Lei et al., 2019 ).…”

Role of AUF1 in modulating the proliferation, migration and senescence of skin cells

“…AUF1 has been suggested to have an inhibitory effect on apoptosis, and upregulated AUF1 contributes to uncontrolled proliferation of liver cells ( 10 ). Previous studies have demonstrated that AUF1 suppresses cellular senescence, and plays roles in anti-aging and maintaining cell proliferation ( 11 , 24 ). However, the cell cycle was not affected by AUF1 in the present study, although AUF1 has been considered to control the mRNA decay of cell cycle-regulatory proteins ( 6 , 25 ).…”

Multiple structural flavors of RNase P in precursor tRNA processing

“…Perhaps this collective bizarreness led to the rapid diversification of mammalian PRORPs. Although few reports proposed the localization of H1 RNA in human mitochondria with roles as a lncRNA (Lee et al, 2021; Puranam & Attardi, 2001; Wang et al, 2010) suggesting prospects of coexistence of RNP and PRORP forms of RNase P in organelles of eukaryotic cells, the existence of an RNA transport machinery in mitochondria has remained speculative and highly controversial (Jeandard et al, 2019; Kim et al, 2017). Early analysis of the phylogenetic distribution of PRORP enzymes suggested that PRORPs are exclusively eukarya‐specific (Howard et al, 2013; Klemm et al, 2016; Lechner et al, 2015).…”