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MicroRNAs01:22

MicroRNAs

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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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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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Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
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Chromatin Structure Regulates pre-mRNA Processing02:41

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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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RNA Structure01:23

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The basic structure of RNA consists of a five-carbon sugar and one of four nitrogenous bases. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
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The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
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A Reporter Assay to Analyze Intronic microRNA Maturation in Mammalian Cells
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Visualizing a protonated RNA state that modulates microRNA-21 maturation.

Jared T Baisden1, Joshua A Boyer1, Bo Zhao1,2

  • 1Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Nature Chemical Biology
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Summary
This summary is machine-generated.

MicroRNA maturation is regulated by pH-dependent structural dynamics. The precursor of microRNA-21 uses an alternative conformation to enhance Dicer processing, revealing a new layer of microRNA biogenesis control.

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • MicroRNAs (miRNAs) are crucial noncoding RNAs regulating gene expression.
  • miRNA biogenesis is a tightly controlled process involving specific protein interactions.
  • Understanding miRNA maturation mechanisms is key to deciphering gene regulation.

Purpose of the Study:

  • To investigate the structural dynamics of precursor microRNA-21 (pre-miR-21).
  • To elucidate the role of these dynamics in Dicer processing and miRNA maturation.
  • To explore pH-dependent regulation of miRNA biogenesis.

Main Methods:

  • Nuclear Magnetic Resonance (NMR) relaxation dispersion spectroscopy.
  • Site-directed mutagenesis.
  • Biochemical assays for Dicer processing.

Main Results:

  • Pre-miR-21 exists as a pH-dependent dynamic ensemble.
  • An alternative conformation involves a protonated adenine-guanine mismatch, sequestering bulged adenine.
  • This conformation significantly enhances Dicer enzyme processing efficiency.

Conclusions:

  • MicroRNA maturation efficiency can be encoded within the intrinsic dynamics of precursor miRNAs.
  • pH-dependent structural ensembles offer a mechanism for regulating miRNA biogenesis.
  • These findings provide insights into cellular responses to environmental stimuli.