Slicing tRNAs to boost functional ncRNA diversity

Gebetsberger, Jennifer; Polacek, Norbert

doi:10.4161/rna.27177

Cited by 222 publications

(226 citation statements)

References 85 publications

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“…A simple explanation is the increased coverage with ultradeep sequencing methods and coverage of any cell type including tumors, many developmental stages, as well as (tumor) cell lines numerous times over (Carninci 2009;Ritz et al 2011;Haas et al 2012;Ho et al 2012;Shah et al 2012;Eswaran et al 2013;Hu et al 2013;Schonberg et al 2013;Yoshihara et al 2013). With all this overabundance, there is a debate raging between those that claim almost any identified transcript and snippet of RNA to be functional (Mattick 2003;Lee et al 2009;Carninci 2010;Kishore et al 2010;Clark et al 2011;Bernstein et al 2012;Kapranov and St Laurent 2012;Khayrullina et al 2012;Gebetsberger and Polacek 2013;Mattick and Dinger 2013) and more conservative voices (Brosius 2005c;Huttenhofer et al 2005;Robinson 2010;van Bakel et al 2010;Graur et al 2013). The writer concurs with the argumentation for spurious and stochastic transcripts (Kowalczyk et al 2012;Jensen et al 2013;Mudge et al 2013), especially as many transcription promoters are bidirectional (Seila et al 2008;Neil et al 2009;Xu et al 2009;Wei et al 2011;Uesaka et al 2014).…”

Section: Did Rna Enter Bubble Territory?mentioning

confidence: 99%

The Persistent Contributions of RNA to Eukaryotic Gen(om)e Architecture and Cellular Function

Brosius

2014

Cold Spring Harbor Perspectives in Biology

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Section: Did Rna Enter Bubble Territory?mentioning

confidence: 99%

The Persistent Contributions of RNA to Eukaryotic Gen(om)e Architecture and Cellular Function

Brosius

2014

Cold Spring Harbor Perspectives in Biology

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“…10,11 tRNAs have further been reported to serve as a source of small functional RNAs. [12][13][14] Numerous tRNA-interacting proteins have recently been proposed, 15 indicating the scope of tRNA biological functions may be far beyond that previously assumed.…”

Section: Introductionmentioning

confidence: 99%

Four-leaf clover qRT-PCR: A convenient method for selective quantification of mature tRNA

et al. 2015

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Transfer RNAs (tRNAs) play a central role in translation and also recently appear to have a variety of other functions in biological processes beyond translation. Here we report the development of Four-Leaf clover qRT-PCR (FL-PCR), a convenient PCR-based method, which can specifically quantify individual mature tRNA species. In FL-PCR, T4 RNA ligase 2 specifically ligates a stem-loop adapter to mature tRNAs but not to precursor tRNAs or tRNA fragments. Subsequent TaqMan qRT-PCR amplifies only unmodified regions of the tRNA-adapter ligation products; therefore, FL-PCR quantification is not influenced by tRNA post-transcriptional modifications. FL-PCR has broad applicability for the quantification of various tRNAs in different cell types, and thus provides a much-needed simple method for analyzing tRNA abundance and heterogeneity.

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“…In many organisms, small RNAs are produced from mature tRNAs or their precursor transcripts not as random degradation products, but as functional molecules involved in many biological processes beyond translation (6)(7)(8). According to the proposed nomenclature (7), tRNA-derived small RNAs identified to date can be classified into two groups: tRNA halves and tRNA-derived fragments.…”

mentioning

confidence: 99%

Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers

Honda

Loher

Shigematsu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

319

464

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Sex hormones and their receptors play critical roles in the development and progression of the breast and prostate cancers. Here we report that a novel type of transfer RNA (tRNA)-derived small RNA, termed Sex HOrmone-dependent TRNA-derived RNAs (SHOTRNAs), are specifically and abundantly expressed in estrogen receptor (ER)-positive breast cancer and androgen receptor (AR)-positive prostate cancer cell lines. SHOT-RNAs are not abundantly present in ER − breast cancer, AR − prostate cancer, or other examined cancer cell lines from other tissues. ER-dependent accumulation of SHOT-RNAs is not limited to a cell culture system, but it also occurs in luminal-type breast cancer patient tissues. SHOT-RNAs are produced from aminoacylated mature tRNAs by angiogenin-mediated anticodon cleavage, which is promoted by sex hormones and their receptors. Resultant 5′-and 3′-SHOT-RNAs, corresponding to 5′-and 3′-tRNA halves, bear a cyclic phosphate (cP) and an amino acid at the 3′-end, respectively. By devising a "cP-RNA-seq" method that is able to exclusively amplify and sequence cP-containing RNAs, we identified the complete repertoire of 5′-SHOT-RNAs. Furthermore, 5′-SHOT-RNA, but not 3′-SHOT-RNA, has significant functional involvement in cell proliferation. These results have unveiled a novel tRNA-engaged pathway in tumorigenesis of hormone-dependent cancers and implicate SHOT-RNAs as potential candidates for biomarkers and therapeutic targets.tRNA | tRNA half | sex hormone | breast cancer | prostate cancer

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Slicing tRNAs to boost functional ncRNA diversity

Cited by 222 publications

References 85 publications

The Persistent Contributions of RNA to Eukaryotic Gen(om)e Architecture and Cellular Function

The Persistent Contributions of RNA to Eukaryotic Gen(om)e Architecture and Cellular Function

Four-leaf clover qRT-PCR: A convenient method for selective quantification of mature tRNA

Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers

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