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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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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
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Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒  small G-proteins consisting of a single domain and large multi-domain G-proteins.
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Long non-coding RNA CCRR controls cardiac conduction via regulating intercellular coupling.

Yong Zhang1, Lihua Sun1, Lina Xuan1

  • 1Department of Pharmacology, State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, P.R. China.

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|October 11, 2018
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Cardiac conduction regulatory RNA (CCRR) acts as an antiarrhythmic long non-coding RNA (lncRNA). Downregulation of CCRR in heart failure worsens cardiac conduction and increases arrhythmia risk, suggesting CCRR replacement therapy.

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Area of Science:

  • Molecular Biology
  • Cardiovascular Biology

Background:

  • Long non-coding RNAs (lncRNAs) are crucial gene expression regulators in biological and pathological processes.
  • Cardiac arrhythmias are often associated with impaired cardiac conduction.

Purpose of the Study:

  • To identify and characterize a novel long non-coding RNA (lncRNA) involved in cardiac conduction and arrhythmia.
  • To elucidate the molecular mechanisms underlying the antiarrhythmic function of CCRR.

Main Methods:

  • Utilized a mouse model of heart failure (HF) and human HF patient samples.
  • Investigated the role of CCRR via gene silencing and overexpression.
  • Analyzed cardiac conduction, intercalated discs, gap junctions, and connexin43 (Cx43) trafficking.

Main Results:

  • CCRR is downregulated in HF, leading to slowed cardiac conduction and increased arrhythmogenicity.
  • CCRR silencing in healthy mice induced arrhythmias and disrupted intercalated discs and gap junctions.
  • CCRR overexpression restored normal cardiac conduction by preventing Cx43 degradation via interaction with CIP85.

Conclusions:

  • Cardiac conduction regulatory RNA (CCRR) functions as an antiarrhythmic lncRNA.
  • CCRR plays a critical role in maintaining cardiac conduction and preventing arrhythmias.
  • CCRR replacement therapy holds potential for treating pathological arrhythmias.