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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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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
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METTL3 Induces AAA Development and Progression by Modulating N6-Methyladenosine-Dependent Primary miR34a Processing.

Lintao Zhong1, Xiang He2, Haoyu Song2

  • 1Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Cardiology, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai 519000, China.

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Methyltransferase-like 3 (METTL3) promotes abdominal aortic aneurysm (AAA) formation by enhancing microRNA-34a maturation. Inhibiting METTL3 may offer a new therapeutic strategy for treating AAA disease.

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Area of Science:

  • Vascular Medicine
  • Epigenetics
  • Molecular Biology

Background:

  • Abdominal aortic aneurysm (AAA) progression is difficult to treat.
  • The role of Methyltransferase-like 3 (METTL3) and its m6A modification in AAA is unknown.

Purpose of the Study:

  • To investigate the role of METTL3 in AAA formation.
  • To elucidate the underlying molecular mechanisms of METTL3 in AAA.

Main Methods:

  • Used apolipoprotein E-deficient (ApoE-/-) and calcium chloride (CaCl2)-induced mouse AAA models.
  • Investigated METTL3 knockdown and overexpression effects on AAA formation.
  • Analyzed the impact of METTL3 on microRNA-34a (miR-34a) maturation and SIRT1 expression.

Main Results:

  • METTL3 knockdown suppressed AAA formation, while overexpression exacerbated it.
  • METTL3 promoted pri-miR-34a maturation via DGCR8, leading to decreased SIRT1 expression and aggravated AAA.
  • miR-34a deficiency or SIRT1 overexpression attenuated AAA formation.

Conclusions:

  • METTL3/m6A-mediated miR-34a maturation is crucial in AAA development.
  • METTL3 represents a potential therapeutic target and diagnostic biomarker for AAA.