IsomiR processing during differentiation of myelogenous leukemic cell line K562 by phorbol ester PMA

Muiwo, Pamchui; Pandey, Priyatama; Ramachandran, Suganthi S.; Bhattacharya, Alok

doi:10.1016/j.gene.2017.10.025

Cited by 4 publications

(6 citation statements)

References 55 publications

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“…Whether changes of isomiR stoichiometry shown here are restricted to phagocytes is unlikely since we saw similar responses in human fibroblasts (Nejad et al 2018a,b), which are functionally very different from phagocytes. In addition, a recent study reported that PMA treatment of the chronic myelocytic leukemia cell line K562 promoted changes of isomiR stoichiometry in 7% of the 133 miRNA families analyzed (Muiwo et al 2018). Similar to what we describe here with LPS, the isoforms of miR-27b-3p were differently impacted by PMA in this study, and the prevalent isoform shifted from the 21 to 20 nt long 3 ′ -isomiR (Muiwo et al 2018).…”

Section: Resultssupporting

confidence: 87%

“…In addition, a recent study reported that PMA treatment of the chronic myelocytic leukemia cell line K562 promoted changes of isomiR stoichiometry in 7% of the 133 miRNA families analyzed (Muiwo et al 2018). Similar to what we describe here with LPS, the isoforms of miR-27b-3p were differently impacted by PMA in this study, and the prevalent isoform shifted from the 21 to 20 nt long 3 ′ -isomiR (Muiwo et al 2018). However, further studies are needed to define whether the broad changes of isomiRs seen in the context of pathogen infection are also seen with other stimuli, and to define how such changes impact miRNA function.…”

Section: Resultsmentioning

confidence: 99%

“…There is increasing evidence that microRNA (miRNA) length variants are differentially expressed between cell types (Juzenas et al 2017), cancer types (Telonis et al 2017), and upon cell stimulation (as seen with stimuli such as PMA [Muiwo et al 2018] or type-I interferon [IFN] [Nejad et al 2018b]). Critically, such length variations from what is considered to be the canonical length (as per its definition in miRbase [Kozomara and Griffiths-Jones 2014]) are not restricted to poorly abundant isoforms.…”

Section: Introductionmentioning

confidence: 99%

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miRNA length variation during macrophage stimulation confounds the interpretation of results: implications for miRNA quantification by RT-qPCR

Pillman

Goodall

Bracken

et al. 2018

RNA

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Most microRNAs (miRNAs) are expressed as a mix of length isoforms (referred to as isomiRs). IsomiR stoichiometry can be differentially impacted upon cell stimulation, as recently evidenced by our group in the context of immune responses induced by type-I interferon (IFN). Here, we revisit published RNA-seq data sets of human and mouse macrophages stimulated with bacterial products at the isomiR level. We demonstrate that for several miRNAs, macrophage stimulation induces changes in isomiR stoichiometry. Critically, we find that changes in miRNA expression can be misinterpreted when miRNAs are quantified by RT-qPCR, as primers directed against canonical miRNA sequences may not equally target the different isomiRs that are regulated endogenously. Beyond the case of phagocyte stimulation, our analyses reinforce the concept that analysis of miRNA expression at the isoform level should become standard practice.

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Section: Resultssupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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miRNA length variation during macrophage stimulation confounds the interpretation of results: implications for miRNA quantification by RT-qPCR

Pillman

Goodall

Bracken

et al. 2018

RNA

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“…Independent reports confirmed our observations that isomiRs can be dynamically regulated [225][226][227], indicating that inducible isomiR processing is not limited to the context of immune responses to infection. A handful of examples support the concept that the length of miRNA ends can directly impact their function [207,[228][229][230], but how this is broadly operating is poorly defined beyond the cases of 5 end variations which impact target recognition (miRNA 5 ends predominantly interact with their target mRNAs).…”

Section: Importantly Trbp Expression Directly Modulates Isomir Cleavage By Dicer As Recently Reported Insupporting

confidence: 87%

Dynamic mRNP Remodeling in Response to Internal and External Stimuli

et al. 2020

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Signal transduction and the regulation of gene expression are fundamental processes in every cell. RNA-binding proteins (RBPs) play a key role in the post-transcriptional modulation of gene expression in response to both internal and external stimuli. However, how signaling pathways regulate the assembly of RBPs with mRNAs remains largely unknown. Here, we summarize observations showing that the formation and composition of messenger ribonucleoprotein particles (mRNPs) is dynamically remodeled in space and time by specific signaling cascades and the resulting post-translational modifications. The integration of signaling events with gene expression is key to the rapid adaptation of cells to environmental changes and stress. Only a combined approach analyzing the signal transduction pathways and the changes in post-transcriptional gene expression they cause will unravel the mechanisms coordinating these important cellular processes.

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“…24 Interestingly, recent studies have shown that one of these 14q32 microRNAs, miR-411, has a 5 0 -isomiR. 25 This miR-411 5 0 -isomiR (ISO-miR-411) has an additional 5 0 adenosine compared to the canonical wild-type miR-411 (WT-miR-411). The isomiR appears to be the result of a single nucleotide shift in DROSHA's cleavage of the primary miR-411 transcript (pri-miR-411) (Figure 1A).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-411 and Its 5′-IsomiR Have Distinct Targets and Functions and Are Differentially Regulated in the Vasculature under Ischemia

et al. 2020

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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 0 end of a microRNA. The exact sequence of a mature microRNA, and thus of its 5 0 and 3 0 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 0 end, forming a so-called 5 0 -isomiR, this results in a shift in the mature microRNA's seed sequence. The role of 5 0 -isomiRs in cardiovascular diseases is still unknown. Here, we characterize the expression and function of the 5 0 -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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IsomiR processing during differentiation of myelogenous leukemic cell line K562 by phorbol ester PMA

Cited by 4 publications

References 55 publications

miRNA length variation during macrophage stimulation confounds the interpretation of results: implications for miRNA quantification by RT-qPCR

miRNA length variation during macrophage stimulation confounds the interpretation of results: implications for miRNA quantification by RT-qPCR

Dynamic mRNP Remodeling in Response to Internal and External Stimuli

MicroRNA-411 and Its 5′-IsomiR Have Distinct Targets and Functions and Are Differentially Regulated in the Vasculature under Ischemia

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