Functions of tRNAs and their pieces beyond translation
In eukaryotes, tRNA genes are massively transcribed by RNA polymerase III. They were long thought to serve an exclusive role in protein translation and supposedly lacked regulatory functions. In recent years however, various connections between tRNAs and cellular pathways beyond genetic translation have been discovered. A new review by Drs Geslain and Eriani presents some aspects of the emerging variety of tasks performed by full length tRNAs as well as their fragments generated by specific nuclease cleavage. The authors discuss the effect of differential expression of tRNAs in healthy tissues as well as their frequent deregulation observed in cancer cells. They also review the central role played by tRNAMet in cell metabolism, proliferation, and response to oxidative stress. Finally they summarize and discuss evidences suggesting that tRNAs are critical sources of short RNAs regulating an ever growing variety of cellular processes including translation initiation, control of genomic retroviral sequences, or RNA interference. With the discovery of new tRNA functions and the appreciation of the extent of their ramifications, the field of tRNA research has reached a new era.
Translation, 2014, Volume 2
Regulation of Translation Dynamic and Neoplastic Conversion by tRNA and Their Pieces
Renaud Geslain, Gilbert Eriani
https://www.landesbioscience.com/journals/translation/article/28586/
RACK-1 regulates let-7 expression and terminal cell differentiation in C. elegans
The let-7 microRNA (miRNA) regulates cell cycle exit and terminal differentiation in the C. elegans heterochronic gene pathway. Low expression of let-7 results in retarded vulva and hypodermal cell development in C. elegans and has been associated with several human cancers. The versatile scaffold protein receptor for activated C kinase 1 (RACK1) has previously been proposed to facilitate recruitment of the miRNA-induced silencing complex (miRISC) to the polysome and to be required for miRNA function in C. elegans and humans. In a new study Dr Shih-Peng Chan and colleagues showed that depletion of C. elegans RACK-1 by RNAi increased let-7 miRNA levels and suppresses the retarded terminal differentiation of lateral hypodermal seam cells in mutants carrying the hypomorphic let-7(n2853) allele or lacking the let-7 family miRNA genes mir-48 and mir-241. Depletion of RACK-1 also increased the levels of precursor let-7 miRNA. When Dicer was knocked down and pre-miRNA processing was inhibited, depletion of RACK-1 still led to increased levels of pre-let-7, suggesting that RACK-1 affects a biogenesis mechanism upstream of Dicer. No changes in the activity of the let-7 promoter or the levels of primary let-7 miRNA were associated with depletion of RACK-1, suggesting that RACK-1 affects let-7 miRNA biogenesis at the post-transcriptional level. Interestingly,rack-1 knockdown also increased the levels of a few other precursor miRNAs. In conclusion, the study results revealed that RACK-1 controls the biogenesis of a subset of miRNAs, including let-7, and in this way plays a role in the heterochronic gene pathway during C. elegans development.
Cell Cycle, June 2014, 13(12): x-y
RACK-1 regulates let-7 microRNA expression and terminal cell differentiation in Caenorhabditis elegans
Yu-De Chu, Wei-Chieh Wang, Shi-An A Chen, Yen-Ting Hsu, Meng-Wei Yeh, Frank J Slack, Shih-Peng Chan
miR941 and miR1247 target gastric cancer cell growth and migration
It is well established that altered expression of microRNA (miRNA) can significantly contribute to cancer development and recent studies have shown that a number of miRNAs may be regulated by DNA methylation. A recent study by Drs Angela Ting, Joo Mi Yi and colleagues, identified miR941 and miR1247 to be transcriptionally silenced by DNA hypermethylation in several gastric cancer cell lines. These miRNAs were also densely methylated in primary gastric cancers but not in normal gastric tissues. Ectopic expression of these 2 miRNAs in AGS gastric cancer cells resulted in suppression of growth and migration. The authors tested genes predicted to be the targets of miR941 and miR1247 and identified 7 and 6 genes, respectively, whose expression in gastric cancer cell lines was significantly downregulated by transfection of miR941 and miR1247 mimics. Some of these genes are known to promote proliferation and invasion, phenotypes we observed upon ectopic expression of the 2 miRNAs. Closer examination of these candidates revealed that downregulation of mRNA corresponds to a decrease in protein levels. The study provides unequivocal evidence that miR941 and miR1247 are transcriptionally regulated by DNA methylation in gastric cancer and that they have tumor suppressor properties through their inhibition of key cancer promoting genes in this context.
Epigenetics, July 2014, 9(7): x-y
Epigenetically regulated MIR941and MIR1247 target gastric cancer cell growth and migration
Joong-Gook Kim, Tae-Oh Kim, Jin-Han Bae, Jae-Woong Shim, Myoung Joo Kang, Kwangmo Yang, Angela H Ting, Joo Mi Yi
https://www.landesbioscience.com/journals/epigenetics/article/29007/
Transcription elongation: mechanisms of regulation of RNA polymerase pausing
Over the past 50 years, the mechanism of transcription by DNA-dependent RNA polymerase has been intensively investigated. Transcription is divided into 3 major stages: initiation, chain elongation and chain termination. In contrast to initiation and termination, occuring at specific DNA sites, elongation involves a gene-scale DNA tracking system which is accompanied by bond-formation at every base pair. Hence specific DNA conformations/ flexibilities, DNA lesions, and DNA-binding proteins are of specific concern in the regulation of elongation. One of the major mechanisms that regulates elongation in all kingdoms of life is sequence-dependent pausing. Regulation of transcription elongation via pausing of RNA polymerase has multiple physiological roles. The pausing mechanism depends on the sequence heterogeneity of the DNA being transcribed, as well as on certain interactions of polymerase with specific DNA sequences. A recent review by Mikhail Kashlev and colleagues describes the mechanism of regulation by introducing the concept of heterogeneity into the previously proposed alternative models of elongation, power stroke and Brownian ratchet. The authors also discuss molecular origins and physiological significances of the heterogeneity.
Transcription, 2014, Volume 5
Transcription elongation: Heterogeneous tracking of RNA polymerase and its biological implications
Masahiko Imashimizu, Nobuo Shimamoto, Taku Oshima, Mikhail Kashlev
https://www.landesbioscience.com/journals/transcription/article/28285/