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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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lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

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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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The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
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Neuronal-expressed microRNA-targeted pseudogenes compete with coding genes in the human brain.

S Barbash1, A Simchovitz1, A S Buchman2

  • 1The Edmond &Lily Safra Center for Brain Sciences and the Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.

Translational Psychiatry
|August 9, 2017
PubMed
Summary
This summary is machine-generated.

Non-coding pseudogenes with microRNA recognition elements (MREs) are involved in brain function and neuronal regulation. These pseudogenes (PSG+MRE) interact with microRNAs and coding transcripts, impacting brain development and potentially mental diseases.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs regulate brain function by binding to microRNA recognition elements (MREs) on target transcripts.
  • The competitive interactions between coding and non-coding transcripts sharing MREs within the microRNA pool are not well understood.

Purpose of the Study:

  • To investigate the role of non-coding pseudogenes carrying MREs (PSG+MRE) in the human brain.
  • To explore the functional involvement and regulatory interactions of PSG+MRE with microRNAs and coding transcripts.

Main Methods:

  • Comparative analysis of pseudogenes with and without MREs (PSG+MRE vs. PSG-MRE) in human temporal lobe neurons.
  • Detection of PSG+MRE in neuronal RNA-induced silencing complexes (RISC).
  • Cell culture experiments to assess co-regulation between PSG+MRE, MRE-sharing coding transcripts, and microRNAs.

Main Results:

  • Duplicated pseudogenes with MREs (PSG+MRE) are evolutionarily conserved and highly expressed in human temporal lobe neurons.
  • PSG+MRE are functional components of neuronal RISC.
  • Bidirectional co-regulation was observed between PSG+MRE and MRE-sharing coding transcripts (often not their parent genes) and targeted microRNAs.
  • Single-nucleotide polymorphisms in PSG+MRE are associated with schizophrenia, bipolar disorder, and autism.

Conclusions:

  • Duplicated pseudogenes with MREs play significant roles in human brain development and cognition.
  • Reciprocal co-regulation between PSG+MRE and MRE-sharing coding transcripts impacts neuronal function.
  • Pseudogene involvement in microRNA regulation may contribute to the etiology of mental diseases.