A nucleolar long "non-coding" RNA encodes a novel protein that functions in response to stress.
A nucleolar long "non-coding" RNA encodes a novel protein that functions in response to stress.
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一种核仁长“非编码”RNA编码一种新的蛋白质，这种蛋白质在应激反应中起作用。
DOI：
10.1073/pnas.2221109120
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发表时间：
2023-02-28
影响因子：
11.1
通讯作者：
Manley, James L.
中科院分区：
文献类型：
--
作者：
Feng, Shuang;Desotell, Anthony;Ross, Alison;Jovanovic, Marko;Manley, James L.
Nucleoli have long been known as the sites of rRNA synthesis and processing and more recently for production of several long non-coding (lnc) RNAs that regulate rRNA transcription and other aspects of cellular function. We now show that one such well-characterized “lncRNA,” known as PAPAS, unexpectedly encodes a 25 KDa protein that we have named RIEP (Ribosomal IGS Encoded Protein). RIEP, which is highly conserved in primates but not present in other species, localizes to mitochondria as well as nucleoli and relocalizes to nuclear regions upon stress, where it functions to prevent stress-induced DNA damage. Our study provides important insights into nucleolar function, unexpected properties of lncRNAs, and possible new connections between mitochondria and nucleoli in response to stress. Certain long non-coding RNAs (lncRNAs) are known to contain small open reading frames that can be translated. Here we describe a much larger 25 kDa human protein, “Ribosomal IGS Encoded Protein” (RIEP), that remarkably is encoded by the well-characterized RNA polymerase (RNAP) II-transcribed nucleolar “promoter and pre-rRNA antisense” lncRNA (PAPAS). Strikingly, RIEP, which is conserved throughout primates but not found in other species, predominantly localizes to the nucleolus as well as mitochondria, but both exogenously expressed and endogenous RIEP increase in the nuclear and perinuclear regions upon heat shock (HS). RIEP associates specifically with the rDNA locus, increases levels of the RNA:DNA helicase Senataxin, and functions to sharply reduce DNA damage induced by heat shock. Proteomics analysis identified two mitochondrial proteins, C1QBP and CHCHD2, both known to have mitochondrial and nuclear functions, that we show interact directly, and relocalize following heat shock, with RIEP. Finally, it is especially notable that the rDNA sequences encoding RIEP are multifunctional, giving rise to an RNA that functions both as RIEP messenger RNA (mRNA) and as PAPAS lncRNA, as well as containing the promoter sequences responsible for rRNA synthesis by RNAP I. Our work has thus not only shown that a nucleolar “non-coding” RNA in fact encodes a protein, but also established a novel link between mitochondria and nucleoli that contributes to the cellular stress response.
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影响因子：
8
作者：
Lindström MS;Jurada D;Bursac S;Orsolic I;Bartek J;Volarevic S
通讯作者：
Volarevic S
影响因子：
14.8
作者：
Rappsilber, Juri;Mann, Matthias;Ishihama, Yasushi
通讯作者：
Ishihama, Yasushi
影响因子：
10.5
作者：
Coelho, PSR;Bryan, AC;Snyder, M
通讯作者：
Snyder, M
影响因子：
16
作者：
Floyd BJ;Wilkerson EM;Veling MT;Minogue CE;Xia C;Beebe ET;Wrobel RL;Cho H;Kremer LS;Alston CL;Gromek KA;Dolan BK;Ulbrich A;Stefely JA;Bohl SL;Werner KM;Jochem A;Westphall MS;Rensvold JW;Taylor RW;Prokisch H;Kim JP;Coon JJ;Pagliarini DJ
通讯作者：
Pagliarini DJ
影响因子：
10.5
作者：
Feng, Shuang;Manley, James L.
通讯作者：
Manley, James L.