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Activating the Chromatin by Noncoding RNAs.

SIGNIFICANCE: The extent and breadth of transcription have recently been uncovered and this has revealed an extensive array of noncoding RNAs (ncRNAs). The biological role and significance of these ncRNAs have been realized and to date it appears that ncRNAs may have many important regulatory functions. ncRNAs are multifaceted and they induce a complexity of different types of transcriptional and posttranscriptional regulation, including gene activation. Recent Advances: Association of ncRNAs with gene activation is an important finding. Not only enhancer RNA (eRNA) but other types of ncRNAs, including small RNA (sRNA), long-noncoding RNA (lncRNA), microRNA (miRNA), and PIWI-associated RNA (piRNA), have also been implicated in gene activation. Interestingly, they often coincide with histone modifications that favor an open chromatin. In addition, these ncRNAs can recruit key factors important for transcription, including RNA polymerase II. They may directly bind the genomic DNA or act as scaffolds; alternatively, they may loop the chromatin to enhance transcription.

CRITICAL ISSUES: Although the role of small activating (sa)RNAs has been considerably studied, the roles of miRNAs and piRNAs in gene activation still need to be substantiated and issues of specificity require further studies.

FUTURE DIRECTIONS: The ncRNA field is coming out of its infancy and we are gaining a global picture of the importance of ncRNAs. However, detailed mechanisms of action of the different ncRNAs are still to be determined. This may reveal novel ways of transcriptional regulation, which will facilitate our ability to utilize these regulatory pathways for research and therapeutic purposes. Antioxid. Redox Signal. 29, 813-831.

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