The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells

Keam, Simon P.; Young, Paul E.; McCorkindale, Alexandra L.; Dang, Thurston H. Y.; Clancy, Jennifer L.; Humphreys, David T.; Preiß, Thomas; Hutvágner, György; Martin, David I. K.; Cropley, Jennifer E.; Suter, Catherine M.

doi:10.1093/nar/gku620

Cited by 127 publications

(132 citation statements)

References 65 publications

Supporting

Mentioning

122

Contrasting

Order By: Relevance

“…Because of the similarity of tsRNAs to piRNAs, we hypothesized and then proved that these molecules can interact with Piwi proteins (24). Interestingly, in a recent report, the Tetrahymena Piwi protein Twi12, essential for growth, was found to be loaded with mature tRNA fragments (25).…”

Section: Ts-4521mentioning

confidence: 98%

Dysregulation of a family of short noncoding RNAs, tsRNAs, in human cancer

Pekarsky

Balatti

Palamarchuk

et al. 2016

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

187

222

View full text Add to dashboard Cite

Chronic lymphocytic leukemia (CLL) is the most common human leukemia, and transgenic mouse studies indicate that activation of the T-cell leukemia/lymphoma 1 (TCL1) oncogene is a contributing event in the pathogenesis of the aggressive form of this disease. While studying the regulation of TCL1 expression, we identified the microRNA cluster miR-4521/3676 and discovered that these two microRNAs are associated with tRNA sequences and that this region can produce two small RNAs, members of a recently identified class of small noncoding RNAs, tRNA-derived small RNAs (tsRNAs). We further proved that miR-3676 and miR-4521 are tsRNAs using Northern blot analysis. We found that, like ts-3676, ts-4521 is down-regulated and mutated in CLL. Analysis of lung cancer samples revealed that both ts-3676 and ts-4521 are down-regulated and mutated in patient tumor samples. Because tsRNAs are similar in nature to piRNAs [P-element-induced wimpy testis (Piwi)-interacting small RNAs], we investigated whether ts-3676 and ts-4521 can interact with Piwi proteins and found these two tsRNAs in complexes containing Piwi-like protein 2 (PIWIL2). To determine whether other tsRNAs are involved in cancer, we generated a custom microarray chip containing 120 tsRNAs 16 bp or more in size. Microarray hybridization experiments revealed tsRNA signatures in CLL and lung cancer, indicating that, like microRNAs, tsRNAs may have an oncogenic and/or tumor-suppressor function in hematopoietic malignancies and solid tumors. Thus, our results show that tsRNAs are dysregulated in human cancer.tsRNAs | ts-4521 | ts-3676

show abstract

Section: Ts-4521mentioning

confidence: 98%

Dysregulation of a family of short noncoding RNAs, tsRNAs, in human cancer

Pekarsky

Balatti

Palamarchuk

et al. 2016

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

187

222

View full text Add to dashboard Cite

show abstract

“…piRNAs are highly expressed in reproductive tissues, but are also expressed in the brain [95], and a normal human plasmaderived exosome had 1.31% piRNAs [96]. Some piRNAs can be associated with HIWI2 in somatic cells including cancer cells [97]. Many piRNAs in exponentially growing or growth-arrested human breast cancer MCF-7 cells have also been identified [70].…”

Section: Piwi-interacting Rnas Are Related To Tumorigenesismentioning

confidence: 99%

Emerging roles for PIWI proteins in cancer

Tan¹,

Liu²,

Liao³

et al. 2015

ABBS

View full text Add to dashboard Cite

It is generally accepted that PIWI proteins are predominately expressed in the germline but absent in somatic tissues. Their best-characterized role is to suppress transposon expression, which ensures genomic stability in the germline. However, increasing evidence has suggested that PIWI proteins are linked to the hallmarks of cancer defined by Weinberg and Hanahan, such as cell proliferation, anti-apoptosis, genomic instability, invasion and metastasis. This provides new possibilities for anticancer therapies through the targeting of PIWI proteins, which may have fewer side effects due to their potential classification as a CTA (cancer/testis antigen). Furthermore, PIWI has been proposed to act as a diagnostic and prognostic marker for many types of cancer, and even to differentiate early-and late-stage cancers. We herein summarize the latest progress in this exciting field, hoping to encourage new investigations of PIWIs in cancer biology that will help to develop new therapeutics for clinical application.

show abstract

“…A growing number of studies have found that piwi proteins in humans and mice, specifically, HIWI, PIWIL2 and PIWIL2-like proteins, are expressed in various types of tumor cells. In addition, piRNAs were also detected in these cells [64,90].…”

Section: Piwi-interacting Rnasmentioning

confidence: 86%

Small Non-Coding RNAs in Regulation of Course and Therapeutic Efficacy in Acute Myeloid Leukemia

Klimenko¹

2018

Myeloid Leukemia

View full text Add to dashboard Cite

Small non-coding RNAs (sncRNAs) are small regulatory molecules, which play key roles in fine-tune of all cell functions. In late 1970s and early 1980s, it was first determined that non-coding RNAs contribute to the cellular regulatory processes. The kingdom of sncRNAs is very numerous and it is clear that functions of different members of this family is different from each other and may be involved in normal and pathologic processes in cell. Recently it was investigated that sncRNAs and long non-coding RNAs play roles in cellular differentiation, proliferation, metabolic processes, bioenergetic regulation, cell death and inter-cellular communications, etc. In embryos, non-coding RNAs control maternal-zygotic transition, the maintenance of pluripotency, the pattering of the body axes, the specification and differentiation of cell types and morphogenesis of organs. Development of hematologic malignancies in humans, their course and regulation of resistance and sensitivity of tumorous cells to therapy are under the control of sncRNAs.

show abstract

The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells

Cited by 127 publications

References 65 publications

Dysregulation of a family of short noncoding RNAs, tsRNAs, in human cancer

Dysregulation of a family of short noncoding RNAs, tsRNAs, in human cancer

Emerging roles for PIWI proteins in cancer

Small Non-Coding RNAs in Regulation of Course and Therapeutic Efficacy in Acute Myeloid Leukemia

Contact Info

Product

Resources

About