The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock

Allen, Tiffany A; Kaenel, Sandra Von; Goodrich, James A.; Kugel, Jennifer F.

doi:10.1038/nsmb813

Cited by 262 publications

(224 citation statements)

References 45 publications

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“…Expression of this RNA is increased up to 100-fold in response to environmental stresses such as heat shock (Liu et al 1995;Allen et al 2004). Coimmunoprecipitation and binding experiments have provided evidence that B2 RNA associates with RNA pol II upon heat shock, and in vivo and in vitro transcription experiments have revealed that B2 RNA inhibits RNA pol II by preventing the formation of active preinitiation complexes Espinoza et al 2004).…”

Section: Mouse B2 Rnamentioning

confidence: 99%

Eukaryotic regulatory RNAs: an answer to the ‘genome complexity’ conundrum

Prasanth¹,

Spector²

2007

Genes Dev.

365

305

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A large portion of the eukaryotic genome is transcribed as noncoding RNAs (ncRNAs). While once thought of primarily as "junk," recent studies indicate that a large number of these RNAs play central roles in regulating gene expression at multiple levels. The increasing diversity of ncRNAs identified in the eukaryotic genome suggests a critical nexus between the regulatory potential of ncRNAs and the complexity of genome organization. We provide an overview of recent advances in the identification and function of eukaryotic ncRNAs and the roles played by these RNAs in chromatin organization, gene expression, and disease etiology.

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Section: Mouse B2 Rnamentioning

confidence: 99%

Eukaryotic regulatory RNAs: an answer to the ‘genome complexity’ conundrum

Prasanth¹,

Spector²

2007

Genes Dev.

365

305

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“…Our laboratory reported that 2 ncRNAs, mouse B2 RNA and human Alu RNA, repress mRNA transcription by binding to Pol II during the cellular heat shock response (3,4). B2 and Alu RNAs are transcribed by RNA polymerase III from short interspersed elements (SINEs) (5).…”

mentioning

confidence: 99%

B2 RNA and Alu RNA repress transcription by disrupting contacts between RNA polymerase II and promoter DNA within assembled complexes

Yakovchuk

Goodrich

Kugel

2009

Proc. Natl. Acad. Sci. U.S.A.

146

135

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Noncoding RNAs (ncRNAs) are now recognized as transregulators of eukaryotic transcription, a role once attributed exclusively to protein factors. Two ncRNAs in mammalian cells have been shown to repress general mRNA transcription by RNA polymerase II (Pol II) in response to heat shock: mouse B2 RNA and human Alu RNA. B2 and Alu RNAs bind directly and tightly to Pol II and co-occupy the promoters of repressed genes along with the polymerase. Here, we identified the molecular mechanism by which mouse B2 RNA and human Alu RNA repress Pol II transcription. Biochemical assays to probe the network of protein-DNA interactions at the promoter revealed that B2 and Alu RNAs prevent Pol II from establishing contacts with the promoter both upstream and downstream of the TATA box during closed complex formation. Disruption of these contacts correlates with transcriptional repression. We conclude that B2 and Alu RNA prevent Pol II from properly engaging the DNA during closed complex formation, resulting in complexes with an altered conformation that are transcriptionally inert. In the absence of its normal contacts with the promoter, Pol II is likely held in these inactive complexes on DNA through interactions with promoter-bound TATA box-binding protein and transcription factor IIB.T ranscription is an intricate biological process in which DNA is copied into RNA; it is the critical first step in gene expression. In eukaryotes, the enzyme RNA polymerase II (Pol II) transcribes protein-encoding genes into mRNA with assistance of general transcription factors (GTFs; specifically TFIIA, TFIID, TFIIB, TFIIF, TFIIE, and TFIIH) that are thought to function at most promoters (1). Transcriptional regulation of specific genes occurs through the remarkably balanced interplay of auxiliary factors such as promoter-specific activators and repressors, coregulators, and chromatin-modifying complexes (1). Traditionally, it was thought that all of these factors were proteins, but now it is becoming clear that noncoding RNAs (ncRNAs) also play important roles in regulating transcription. Indeed, diverse ncRNAs have been identified as regulators of nearly every step in the process of mRNA transcription from controlling chromatin structure through regulating transcript elongation (2).Our laboratory reported that 2 ncRNAs, mouse B2 RNA and human Alu RNA, repress mRNA transcription by binding to Pol II during the cellular heat shock response (3, 4). B2 and Alu RNAs are transcribed by RNA polymerase III from short interspersed elements (SINEs) (5). Upon heat shock, the levels of B2 RNA and Alu RNA increase (6, 7) and they function as general repressors of mRNA transcription (3, 4). Biochemical experiments showed that B2 and Alu RNAs bind directly to core Pol II with low nM affinity (4, 8). Other SINE RNAs have been identified in mammalian cells, including mouse B1 RNA and human scAlu RNA (5), the latter of which is likely derived from cleavage of full-length Alu RNA (9). The biological functions for B1 and scAlu RNAs are not known. In vitro both of...

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“…B2 RNA is synthesized after heat shock and specifically binds polymerase II and inhibits transcription. (11,12) Thus, selective pressure as a factor maintaining, at least, some ''functionless'' repeats in the eukaryotic genome should not be neglected. The functional role of non-conventional classes of non-coding RNAs was reviewed recently by Mattick.…”

Section: Introductionmentioning

confidence: 99%

The Y chromosome as a target for acquired and amplified genetic material in evolution

2005

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SummaryThe special properties of the Y chromosome stem form the fact that it is a non-recombining degenerate derivative of the X chromosome. The absence of homologous recombination between the X and the Y chromosome leads to gradual degeneration of various Y chromosome genes on an evolutionary timescale. The absence of recombination, however, also favors the accumulation of transposable elements on the Y chromosome during its evolution, as seen with both Drosophila and mammalian Y chromosomes. Alongside these processes, the acquisition and amplification of autosomal male benefit genes occur. This review will focus on recent studies that reveal the autosome-acquired genes on the Y chromosome of both Drosophila and humans. The evolution of the acquired and amplified genes on the Y chromosome is also discussed. Molecular and comparative analyses of Y-linked repeats in the Drosophila melanogaster genome demonstrate that there was a period of their degeneration followed by a period of their integration into RNAi silencing, which was beneficial for male fertility. Finally, the function of non-coding RNA produced by amplified Y chromosome genetic elements will be discussed.

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The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock

Cited by 262 publications

References 45 publications

Eukaryotic regulatory RNAs: an answer to the ‘genome complexity’ conundrum

Eukaryotic regulatory RNAs: an answer to the ‘genome complexity’ conundrum

B2 RNA and Alu RNA repress transcription by disrupting contacts between RNA polymerase II and promoter DNA within assembled complexes

The Y chromosome as a target for acquired and amplified genetic material in evolution

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