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RNA polymerase (RNAP) carries out DNA-dependent RNA synthesis in both bacteria and eukaryotes. Bacteria do not have a membrane-bound nucleus. So, transcription and translation occur simultaneously, on the same DNA template.
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Transcription Attenuation in Prokaryotes02:42

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Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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MicroRNAs01:22

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
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Transcriptional Regulation: Riboswitches01:23

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lncRNA - Long Non-coding RNAs02:39

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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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Analysis of Termination of Transcription Using BrUTP-strand-specific Transcription Run-on TRO Approach
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Analysis of Termination of Transcription Using BrUTP-strand-specific Transcription Run-on TRO Approach

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Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs.

Ashish Dhir1, Somdutta Dhir1, Nick J Proudfoot1

  • 1Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

Nature Structural & Molecular Biology
|March 3, 2015
PubMed
Summary
This summary is machine-generated.

Most long noncoding RNAs containing microRNAs (miRNAs) are terminated by Microprocessor cleavage, not polyadenylation. This RNase III-mediated process prevents transcriptional readthrough and interference with other genes.

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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • RNA Processing

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression at the post-transcriptional level.
  • Mammalian miRNA biogenesis involves the Microprocessor complex for cotranscriptional cleavage of RNA polymerase II (Pol II) transcripts.
  • While many miRNAs are intronic, a significant portion originates from long noncoding RNAs (lncRNAs), with poorly understood processing mechanisms.

Purpose of the Study:

  • To investigate the transcript processing and termination mechanisms of lncRNAs containing miRNAs (lnc-pri-miRNAs).
  • To determine if lnc-pri-miRNAs utilize the canonical cleavage-and-polyadenylation pathway for termination.
  • To elucidate the role of the Microprocessor complex in lnc-pri-miRNA processing and its impact on gene expression.

Main Methods:

  • Detailed characterization of the liver-specific lnc-pri-miR-122 transcript.
  • Genome-wide analysis of lnc-pri-miRNA processing in human cell lines.
  • Assessment of Microprocessor complex activity and its effect on transcription termination.

Main Results:

  • Most lnc-pri-miRNAs are not terminated by the canonical cleavage-and-polyadenylation pathway.
  • Microprocessor cleavage serves as the primary termination mechanism for lnc-pri-miRNAs.
  • Inactivation of the Microprocessor complex results in extensive transcriptional readthrough of lnc-pri-miRNAs.
  • Transcriptional readthrough interferes with the expression of downstream genes.

Conclusions:

  • A novel RNase III-mediated, polyadenylation-independent mechanism for Pol II transcription termination in mammalian cells is defined.
  • Microprocessor-dependent termination is crucial for preventing transcriptional interference from lnc-pri-miRNAs.
  • This finding reveals a new layer of gene regulation involving lncRNA processing and transcription termination.