Structure of noncoding RNA is a determinant of function of RNA binding proteins in transcriptional regulation

Takanori Oyoshi,Riki Kurokawa

doi:10.1186/2045-3701-2-1

Takanori Oyoshi, Riki Kurokawa

Open Access

https://doi.org/10.1186/2045-3701-2-1

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Abstract

The majority of the noncoding regions of mammalian genomes have been found to be transcribed to generate noncoding RNAs (ncRNAs), resulting in intense interest in their biological roles. During the past decade, numerous ncRNAs and aptamers have been identified as regulators of transcription. 6S RNA, first described as a ncRNA in E. coli, mimics an open promoter structure, which has a large bulge with two hairpin/stalk structures that regulate transcription through interactions with RNA polymerase. B2 RNA, which has stem-loops and unstructured single-stranded regions, represses transcription of mRNA in response to various stresses, including heat shock in mouse cells. The interaction of TLS (translocated in liposarcoma) with CBP/p300 was induced by ncRNAs that bind to TLS, and this in turn results in inhibition of CBP/p300 histone acetyltransferase (HAT) activity in human cells. Transcription regulator EWS (Ewing's sarcoma), which is highly related to TLS, and TLS specifically bind to G-quadruplex structures in vitro. The carboxy terminus containing the Arg-Gly-Gly (RGG) repeat domains in these proteins are necessary for cis-repression of transcription activation and HAT activity by the N-terminal glutamine-rich domain. Especially, the RGG domain in the carboxy terminus of EWS is important for the G-quadruplex specific binding. Together, these data suggest that functions of EWS and TLS are modulated by specific structures of ncRNAs.

Highlights

Gene silencing has emerged as one of the major functions of short double stranded noncoding RNAs that are generated by specific processing machinery
Substitution of the phenylalanines in the RGG domain in EWS eliminated almost completely G-quadruplex bindings. These findings indicate that the phenylalanines and guanidinium groups of the arginines in RGG domain of EWS are important for binding of EWS to the G-quadruplex
Folding of RNA into divergent structures is constrained by specific RNA sequences under physiological conditions

Summary

Introduction

Gene silencing has emerged as one of the major functions of short double stranded noncoding RNAs (ncRNAs) that are generated by specific processing machinery. Recruitment of TLS appeared to be dependent on its binding to ncRNAs transcribed from promoter regions of the cyclin D1 gene Transcription of these promoter-associated ncRNAs was induced by ionizing radiation, enhancing TLS recruitment and reducing cyclin D1 expression. TERRA, G-quadruplex RNA, binds to transcriptional factor EWS EWS is homologous to TLS and TAF15 These three proteins form the TET family (Figure 3). Binding experiments showed that the carboxy-terminal RGG domain of EWS bound to G-quadruplex RNA, whereas the proteins containing the N-terminal of the glutamine-rich domain, RRM, ZnF and other RGG domains did not [60]. Enzymic methylation of Arg by protein arginine N-methyltransferase (PRMT) 3 reduced the binding RGG domain of EWS to G-quadruplexes but increased its binding to single-strand DNA and RNA. These data might contribute to understanding of the nucleic acids binding specificity of RNAbinding proteins containing RGG domains

Conclusions

48. Rauscher FJ III