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DICER1 Loss and Alu RNA Induce Age-Related Macular Degeneration via the NLRP3 Inflammasome and MyD88
TLDR
It is shown that DICER1 deficit or Alu RNA exposure activates the NLRP3 inflammasome and triggers TLR-independent MyD88 signaling via IL18 in the RPE and reveals a function of the inflammaome outside the immune system and an immunomodulatory action of mobile elements. Expand
Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock.
TLDR
It is shown that human Alu RNA, transcribed from short interspersed elements (SINEs), is a transacting transcriptional repressor during the cellular heat shock response. Expand
XPB, a subunit of TFIIH, is a target of the natural product triptolide.
TLDR
It is reported that triptolide covalently binds to human XPB, a subunit of the transcription factor TFIIH, and inhibits its DNA-dependent ATPase activity, which leads to the inhibition of RNA polymerase II-mediated transcription and likely nucleotide excision repair. Expand
DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration
TLDR
Findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness. Expand
The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock
TLDR
During the heat shock response in mouse cells, a small noncodingRNA polymerase III transcript, B2 RNA, associates with RNA polymerase II and represses transcription of specific mRNA genes, defining a unique transcriptional regulatory mechanism involving an RNA regulator and revealing how mRNA transcription is repressed upon heat shock. Expand
B2 RNA binds directly to RNA polymerase II to repress transcript synthesis
TLDR
The studies describe a previously unobserved mechanism of transcriptional repression by a small RNA and suggest that B2 RNA associates with Pol II at promoters in heat shocked cells to actively inhibit transcription. Expand
Non-coding-RNA regulators of RNA polymerase II transcription
Several non-coding RNAs (ncRNAs) that regulate eukaryotic mRNA transcription have recently been discovered. Their mechanisms of action and biological roles are extremely diverse, which indicatesExpand
Characterization of the structure, function, and mechanism of B2 RNA, an ncRNA repressor of RNA polymerase II transcription.
TLDR
Results support a model in which RNA polymerase II contains a high-affinity ncRNA docking site to which a distinct region of B2 RNA binds, thereby allowing another region of the RNA to repress transcription. Expand
Binding and Kinetics for Molecular Biologists
1. Performing quantitative experiments with biomolecules 2. Affinity constants 3. Cooperativity in binding 4. Rate constants for binding and dissociation 5. Kinetics of regulation and cooperativityExpand
B2 RNA and Alu RNA repress transcription by disrupting contacts between RNA polymerase II and promoter DNA within assembled complexes
TLDR
It is concluded 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. Expand
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