Collision events between RNA polymerases in convergent transcription studied by atomic force microscopy

Crampton, Neal; Bonass, William A.; Kirkham, Jennifer; Rivetti, Claudio; Thomson, Neil H.

doi:10.1093/nar/gkl668

Cited by 108 publications

(104 citation statements)

References 40 publications

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“…Our results are consistent with the transcriptional collision model that has been proposed following the analyses of adjacent transcripts and cis -NATs in yeast (Puig et al 1999;Prescott and Proudfoot 2002) and the observation of the collision of RNA polymerases by atomic force microscopy (Crampton et al 2006). RNA polymerases bind to the upstream regions of genes and synthesize mRNAs, moving toward the 39-ends of the genes.…”

Section: à15supporting

confidence: 91%

“…This suggested that RNA polymerases did not stop at the terminator of the upstream transcript and affected the transcription of the downstream transcript. Recently, the collision of Escherichia coli RNA polymerases was observed by atomic force microscopy (Crampton et al 2006). This observation showed that RNA polymerases do not pass each other or displace one another, but instead stall against each other.…”

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confidence: 99%

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Transcriptional Interferences in cis Natural Antisense Transcripts of Humans and Mice

et al. 2007

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For a significant fraction of mRNAs, their expression is regulated by other RNAs, including cis natural antisense transcripts (cis -NATs) that are complementary mRNAs transcribed from opposite strands of DNA at the same genomic locus. The regulatory mechanism of mRNA expression by cis -NATs is unknown, although a few possible explanations have been proposed. To understand this regulatory mechanism, we conducted a large-scale analysis of the currently available data and examined how the overlapping arrangements of cis -NATs affect their expression level. Here, we show that for both human and mouse the expression level of cis -NATs decreases as the length of the overlapping region increases. In particular, the proportions of the highly expressed cis -NATs in all cis -NATs examined were $36 and 47% for human and mouse, respectively, when the overlapping region was ,200 bp. However, both proportions decreased to virtually zero when the overlapping regions were .2000 bp in length. Moreover, the distribution of the expression level of cis -NATs changes according to different types of the overlapping pattern of cis -NATs in the genome. These results are consistent with the transcriptional collision model for the regulatory mechanism of gene expression by cis -NATs.

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Section: à15supporting

confidence: 91%

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confidence: 99%

Transcriptional Interferences in cis Natural Antisense Transcripts of Humans and Mice

et al. 2007

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“…Second, antisense mRNAs were suggested to promote the methylation of sense mRNA promoters. And third, the formation of double-stranded RNA hybrids may interfere with further mRNA processing (Wutz et al, 1997;Lai, 2002;Prescott and Proudfoot, 2002;Tufarelli et al, 2003;Lavorgna et al, 2004;Crampton et al, 2006). These models are not mutually exclusive, and more than one of them may apply to the situation of p53 and WRAP53.…”

Section: Discussionmentioning

confidence: 99%

Anthracyclines induce the accumulation of mutant p53 through E2F1-dependent and -independent mechanisms

Bug

Dobbelstein

2011

Oncogene

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Mutant p53 frequently accumulates in cancer cells and promotes tumor cell invasion, as part of its gain of function. Its accumulation is partially due to enhanced stability, but little is known about how the mRNA levels of mutant p53 can be regulated. Likewise, the impact of cancer therapy on the levels of mutant p53 is poorly understood. We show here that the anthracyclines doxorubicin, daunorubicin and epirubicin further increase the amounts of mutant p53 mRNA and protein in cancer cells. Moreover, we show for the first time that the transcription factor E2F1 associates with the promoter DNA of TP53. Upon genotoxic treatment, E2F1 contributed to the expression of mutant p53, both directly and through induction of TAp73. In contrast, the anthracycline idarubicin and also another topoisomerase inhibitor, etoposide, failed to increase the levels of p53 mRNA, despite their ability to induce the synthesis of TAp73 mRNA. Instead, a natural antisense transcript of TP53, WRAP53, was strongly augmented by idarubicin and etoposide, but only less so by the other anthracyclines under study. RNA corresponding to the first exon of WRAP53 was mainly found in cell nuclei and it reduced the levels of mutant p53. Taken together, this suggests a reciprocal activation pattern of TP53 and WRAP53 by different chemotherapeutics. Reducing the levels of mutant p53 by small-interfering RNA increased chemosensitivity, and idarubicin prevented cell survival more efficiently than the mutant p53-inducing doxorubicin. We conclude that even closely related anthracyclines induce the synthesis of different, opposing transcripts from the TP53 locus. When using these drugs for cancer therapy, the increased levels of mutant p53 may augment its gain of function and thus favor unwanted chemoresistance and tumor progression.

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“…While this phenomenon has been observed in bacteria (Crampton et al 2006) and budding yeast (Prescott and Proudfoot 2002), none has been reported in mammals. However, computational analyses of genes with NATs have found an anticorrelation between the length of overlap and the expression levels of SAS pairs (i.e., the greater the overlap is, the lower the expression of either transcript) (Osato et al 2007), consistent with a transcriptional collision model in which convergent transcripts sterically hinder transcription of one another.…”

Section: Transcript or Act Of Transcription?mentioning

confidence: 92%

Long Noncoding RNAs: Past, Present, and Future

2013

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Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. lncRNAs of all kinds have been implicated in a range of developmental processes and diseases, but knowledge of the mechanisms by which they act is still surprisingly limited, and claims that almost the entirety of the mammalian genome is transcribed into functional noncoding transcripts remain controversial. At the same time, a small number of well-studied lncRNAs have given us important clues about the biology of these molecules, and a few key functional and mechanistic themes have begun to emerge, although the robustness of these models and classification schemes remains to be seen. Here, we review the current state of knowledge of the lncRNA field, discussing what is known about the genomic contexts, biological functions, and mechanisms of action of lncRNAs. We also reflect on how the recent interest in lncRNAs is deeply rooted in biology's longstanding concern with the evolution and function of genomes.T HE past several years have witnessed a steep rise of interest in the study of lncRNAs. Almost on a weekly basis, it seems that a new lncRNA is found to be up-or downregulated in a particular disease, or a new class of noncoding transcripts is uncovered by a transcriptomic study, or a new article heralds a paradigm shift that lncRNAs will bring to our understanding of biology. Without a doubt, the advent of sensitive, high-throughput genomic technologies such as microarrays and next-generation sequencing (NGS) has resulted in an unprecedented ability to detect novel transcripts, the vast majority of which seem not to be derived from annotated protein-coding genes. Despite this explosion of data, however, surprisingly little is known about how lncRNAs function, how many different types of lncRNAs exist, or even whether most of them carry biological significance.In this review, we focus on recently discovered lncRNAs of .200 nt, place these new discoveries in historical context, and outline areas where additional work is needed. The review does not cover "classic" ncRNAs such as ribosomal (r) RNAs, ribozymes, transfer (t)RNAs, small nuclear (sn)RNAs, small nucleolar (sno)RNAs, and telomere-associated RNAs (TERC, TERRA); nor does it cover small ncRNAs such as microRNAs (miRNAs), endogenous small interfering (endo-si)RNAs that participate in RNA interference (RNAi), and Piwi-associated (pi)RNAs. We refer readers to the many

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Collision events between RNA polymerases in convergent transcription studied by atomic force microscopy

Cited by 108 publications

References 40 publications

Transcriptional Interferences in cis Natural Antisense Transcripts of Humans and Mice

Transcriptional Interferences in cis Natural Antisense Transcripts of Humans and Mice

Anthracyclines induce the accumulation of mutant p53 through E2F1-dependent and -independent mechanisms

Long Noncoding RNAs: Past, Present, and Future

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