A population of tRNA-derived small RNAs is actively produced in Trypanosoma cruzi and recruited to specific cytoplasmic granules

García-Silva, María Rosa; Frugier, Magali; Tosar, Juan Pablo; Correa-Dominguez, Alejandro; Alves, Lysangela Ronalte; Parodi-Talice, Adriana; Rovira, Carlos; Robello, Carlos; Goldenberg, Samuel; Cayota, Alfonso

doi:10.1016/j.molbiopara.2010.02.003

Cited by 93 publications

(104 citation statements)

References 43 publications

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“…1A and Tables S1 and S2). The 33-nt peak reads mapped primarily to structural RNA loci (62% of mapped reads) (Table S2), similar to an sRNA class described in many eukaryotes, including trypanosomes and Leishmania lacking the RNAi pathway (41)(42)(43)(44). In contrast, reads from the 23-nt peak showed properties similar to AGO1-bound siRNAs (39), including their size and the presence of one to two untemplated nucleotides at the 3′ end in about 21% of the reads (Fig.…”

Section: Resultsmentioning

confidence: 74%

“…We identified two populations of sRNA in Lbr and Lgy. The less abundant 33-nt sRNAs mapped primarily to genes encoding structural RNAs (Table S2), as seen in other organisms, including trypanosomatids (41)(42)(43)(44). In contrast, the more abundant 23-nt sRNA fraction exhibited properties similar to authentic AGO1-bound Lbr siRNAs (39), including size, the presence of 3′ untemplated bases at the same frequency (∼20%), and mapping primarily to transposable elements and repetitive sequences ( Fig.…”

Section: Discussionmentioning

confidence: 77%

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Tilting the balance between RNA interference and replication eradicatesLeishmaniaRNA virus 1 and mitigates the inflammatory response

Brettmann

Shaik

Zangger

et al. 2016

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

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Many Leishmania (Viannia) parasites harbor the double-stranded RNA virus Leishmania RNA virus 1 (LRV1), which has been associated with increased disease severity in animal models and humans and with drug treatment failures in humans. Remarkably, LRV1 survives in the presence of an active RNAi pathway, which in many organisms controls RNA viruses. We found significant levels (0.4 to 2.5%) of small RNAs derived from LRV1 in both Leishmania braziliensis and Leishmania guyanensis, mapping across both strands and with properties consistent with Dicer-mediated cleavage of the dsRNA genome. LRV1 lacks cis-or trans-acting RNAi inhibitory activities, suggesting that virus retention must be maintained by a balance between RNAi activity and LRV1 replication. To tilt this balance toward elimination, we targeted LRV1 using long-hairpin/stem-loop constructs similar to those effective against chromosomal genes. LRV1 was completely eliminated, at high efficiency, accompanied by a massive overproduction of LRV1-specific siRNAs, representing as much as 87% of the total. For both L. braziliensis and L. guyanensis, RNAi-derived LRV1-negative lines were no longer able to induce a Tolllike receptor 3-dependent hyperinflammatory cytokine response in infected macrophages. We demonstrate in vitro a role for LRV1 in virulence of L. braziliensis, the Leishmania species responsible for the vast majority of mucocutaneous leishmaniasis cases. These findings establish a targeted method for elimination of LRV1, and potentially of other Leishmania viruses, which will facilitate mechanistic dissection of the role of LRV1-mediated virulence. Moreover, our data establish a third paradigm for RNAi-viral relationships in evolution: one of balance rather than elimination.dsRNA virus | protozoan parasite | endosymbiont | trypanosomatid protozoa | microbial pathogenesis

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Section: Resultsmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 77%

Tilting the balance between RNA interference and replication eradicatesLeishmaniaRNA virus 1 and mitigates the inflammatory response

Brettmann

Shaik

Zangger

et al. 2016

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

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show abstract

“…However, total amounts of fulllength tRNAs are not significantly changed by small tRNA processing as judged by Northern blots, suggesting that this phenomenon may not affect the role of tRNAs in protein translation. Also, we recently showed that in unicellular eukaryotes 5 0 and 3 0 tRNA halves are recruited to different, well-defined granules in the cell, indicating that tRNA halves are recruited to specific cytoplasmic structures (67).…”

Section: More Small Rna Regulatory Pathways In Sight Do They Have a mentioning

confidence: 98%

MicroRNAs and other small silencing RNAs in cancer

2010

Self Cite

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SummarySmall noncoding RNAs are key controllers of cellular function, and their deregulation can lead to cancer development and metastatic evolution. This review summarizes the most important examples of small RNAs involved in human cancer and discusses their clinical use as biomarkers and drug targets for diagnosis, prognosis, and treatment of cancer. We also describe the possible mechanisms underlying small RNA-mediated transformation and outline the future describing new small RNA families with great potential in cancer biology.

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“…However, Lee et al (32) reported the successful siRNA knockdown of 3′-trailer-derived tRNA fragments without affecting pre-tRNA levels. Moreover, Garcia-Silva et al (33) succeeded in selectively staining tRNA fragments without obtaining signals from mature tRNAs by avoiding the denaturation step in their modified FISH method. Considering these reports and the fact that mature aminoacylated tRNAs form rigid L-shaped tertiary structures and tightly bind to an elongation factor in the cytoplasm, we assumed that siRNAs targeting SHOT-RNAs could preferably function toward SHOT-RNAs without greatly affecting mature tRNAs.…”

Section: Abundant Accumulation Of Trna Halves In Specific Breast Andmentioning

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.

310

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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A population of tRNA-derived small RNAs is actively produced in Trypanosoma cruzi and recruited to specific cytoplasmic granules

Cited by 93 publications

References 43 publications

Tilting the balance between RNA interference and replication eradicatesLeishmaniaRNA virus 1 and mitigates the inflammatory response

Tilting the balance between RNA interference and replication eradicatesLeishmaniaRNA virus 1 and mitigates the inflammatory response

MicroRNAs and other small silencing RNAs in cancer

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

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