[HTML][HTML] MicroRNA-411 and Its 5′-IsomiR have distinct targets and functions and are differentially regulated in the vasculature under ischemia
RVCT van der Kwast, T Woudenberg, PHA Quax… - Molecular Therapy, 2020 - cell.com
Molecular Therapy, 2020•cell.com
MicroRNAs are posttranscriptional regulators of gene expression. As microRNAs can target
many genes simultaneously, microRNAs can regulate complex multifactorial processes,
including post-ischemic neovascularization, a major recovery pathway in cardiovascular
disease. MicroRNAs select their target mRNAs via full complementary binding with their
seed sequence, ie, nucleotides 2–8 from the 5′ end of a microRNA. The exact sequence of
a mature microRNA, and thus of its 5′ and 3′ ends, is determined by two sequential …
many genes simultaneously, microRNAs can regulate complex multifactorial processes,
including post-ischemic neovascularization, a major recovery pathway in cardiovascular
disease. MicroRNAs select their target mRNAs via full complementary binding with their
seed sequence, ie, nucleotides 2–8 from the 5′ end of a microRNA. The exact sequence of
a mature microRNA, and thus of its 5′ and 3′ ends, is determined by two sequential …
MicroRNAs are posttranscriptional regulators of gene expression. As microRNAs can target many genes simultaneously, microRNAs can regulate complex multifactorial processes, including post-ischemic neovascularization, a major recovery pathway in cardiovascular disease. MicroRNAs select their target mRNAs via full complementary binding with their seed sequence, i.e., nucleotides 2–8 from the 5′ end of a microRNA. The exact sequence of a mature microRNA, and thus of its 5′ and 3′ ends, is determined by two sequential cleavage steps of microRNA precursors, Drosha/DGCR8 and Dicer. When these cleavage steps result in nucleotide switches at the 5′ end, forming a so-called 5′-isomiR, this results in a shift in the mature microRNA's seed sequence. The role of 5′-isomiRs in cardiovascular diseases is still unknown. Here, we characterize the expression and function of the 5′-isomiR of miR-411 (ISO-miR-411). ISO-miR-411 is abundantly expressed in human primary vascular cells. ISO-miR-411 has a different "targetome" from WT-miR-411, with only minor overlap. The ISO-miR-411/WT-miR-411 ratio is downregulated under acute ischemia, both in cells and a murine ischemia model, but is upregulated instead in chronically ischemic human blood vessels. ISO-miR-411 negatively influences vascular cell migration, whereas WT-miR-411 does not. Our data demonstrate that isomiR formation is a functional pathway that is actively regulated during ischemia.
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