Transcription control by long non-coding RNAs

Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
Transcription 03/2012; 3(2):78-86. DOI: 10.4161/trns.19349
Source: PubMed

ABSTRACT Non-coding RNAs have been found to regulate many cellular processes and thus expand the functional genetic repertoire contained within the genome. With the recent advent of genomic tools, it is now evident that these RNA molecules play central regulatory roles in many transcriptional programs. Here we discuss how they are targeted to promoters in several cases and how they operate at specific points in the transcription cycle to precisely control gene expression.


Available from: Iván D'Orso, Oct 28, 2014
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Antisense transcription, considered until recently as transcriptional noise, is a very common phenomenon in human and eukaryotic transcriptomes, operating in two ways based on whether the antisense RNA acts in cis or in trans. This process can generate long non-coding RNAs (lncRNAs), one of the most diverse classes of cellular transcripts, which have demonstrated multifunctional roles in fundamental biological processes, including embryonic pluripotency, differentiation and development. Antisense lncRNAs have been shown to control nearly every level of gene regulation-pretranscriptional, transcriptional and posttranscriptional-through DNA-RNA, RNA-RNA or protein-RNA interactions. This review is centered on functional studies of antisense lncRNA-mediated regulation of neighboring gene expression. Specifically, it addresses how these transcripts interact with other biological molecules, nucleic acids and proteins, to regulate gene expression through chromatin remodeling at the pretranscriptional level and modulation of transcriptional and post-transcriptional processes by altering the sense mRNA structure or the cellular compartmental distribution, either in the nucleus or the cytoplasm.
    International Journal of Molecular Sciences 02/2015; 16(2):3251-3266. DOI:10.3390/ijms16023251 · 2.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal cancer (CRC) is one of the most common cancers worldwide. Long non-coding RNAs (lncRNAs) have been shown to play important regulatory roles in cancer biology, and functional lncRNAs can be used for cancer diagnosis and prognosis. One lncRNA that has attracted significant attention is urothelial carcinoma-associated 1 (UCA1), which is significantly up-regulated in most tumour tissues and cancer cells. However, the contributions of UCA1 to CRC remain largely unknown. Thus, the aim of the current study was to investigate the clinical significance and biological function of UCA1 in CRC.First, we evaluated whether UCA1 is detectable or altered in CRC tissues or cell lines compared to adjacent normal tissues or normal cell lines by quantitative real-time polymerase chain reaction. The potential relationship between UCA1 levels in tumour tissues and the clinicopathological features of CRC was then investigated. Finally, we assessed whether UCA1 influences cell proliferation, apoptosis, cell cycle distribution and migration in vitro.Our results demonstrated that UCA1 levels were markedly increased in CRC tissues and cells compared to controls, and this high level of UCA1 expression was significantly correlated with larger tumour size, less differentiated histology and greater tumour depth. In addition, patients with high UCA1 expression had a significantly poorer prognosis than those with low UCA1 expression. Moreover, UCA1 was found to influence the proliferation, apoptosis and cell cycle progression of CRC cells. These data suggest an important role for UCA1 in the molecular aetiology of CRC and suggest a potential application for UCA1 in CRC diagnosis, progression and therapy.
    Pathology 06/2014; 46(5). DOI:10.1097/PAT.0000000000000125 · 2.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Transcription factors regulate eukaryotic RNA polymerase II (Pol II) activity by assembling and remodeling complexes at multiple steps in the transcription cycle. In HIV, we previously proposed a two-step model where the viral Tat protein first preassembles at the promoter with an inactive P-TEFb:7SK snRNP complex and later transfers P-TEFb to TAR on the nascent transcript, displacing the inhibitory snRNP and resulting in Pol II phosphorylation and stimulation of elongation. It is unknown how the Tat:P-TEFb complex transitions to TAR to activate the P-TEFb kinase. Here, we show that P-TEFb artificially recruited to the nascent transcript is not competent for transcription but rather remains inactive due to its assembly with the 7SK snRNP. Tat supplied in trans is able to displace the kinase inhibitor Hexim1 from the snRNP and activate P-TEFb, thereby uncoupling Tat requirements for kinase activation and TAR binding. By combining comprehensive mutagenesis of Tat with multiple cell-based reporter assays that probe the activity of Tat in different arrangements, we genetically defined a transition step in which preassembled Tat:P-TEFb complexes switch to TAR. We propose that a conserved network of residues in Tat has evolved to control this transition and thereby switch the host elongation machinery to viral transcription.
    Molecular and Cellular Biology 12/2012; 32(23). DOI:10.1128/MCB.00206-12 · 5.04 Impact Factor