ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2025
Characterization and molecular targeting of CFIm25 (NUDT21/CPSF5) mRNA using miRNAs.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Functional characterization of snoRNA-derived RNA (sdRNA) expression in healthy hematopoiesis and acute myeloid leukemia.Leukemia · 2026Article
- Hyperosmotic stress-induced redistribution of pre-mRNA cleavage factor I subunits is associated with shifts in alternative polyadenylation.FEBS open bio · 2026Article
- Systematic dysregulation of immune-related alternative polyadenylation in systemic lupus erythematosus contributes to patient stratification.Journal of translational autoimmunity · 2026Article
- Alternative polyadenylation releases PCBP1-mediated suppression of CFIm25 during macrophage differentiation.FEBS letters · 2026Article
- The alternative polyadenylation regulator CFIm25 promotes macrophage differentiation and activates the NF-κB pathway.Cell communication and signaling : CCS · 2025Article
- Characterization and molecular targeting of CFIm25 (NUDT21/CPSF5) mRNA using miRNAs.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Plasma exosomal miR-30b-5p attenuates neuroinflammation in a rat model of autism spectrum disorder.Frontiers in psychiatry · 2025Article
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3 authors.
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Abstract
Changes in protein levels of the mammalian cleavage factor, CFIm25, play a role in regulating pathological processes including neural dysfunction, fibrosis, and tumorigenesis. However, despite these effects, little is known about how CFIm25 (NUDT21) expression is regulated at the RNA level. A potential regulator of NUDT21 mRNA are small non-coding microRNAs (miRNAs). In general, miRNAs bind to the 3'untranslated regions (3'UTRs) and can target the bound mRNA for degradation or inhibit translation thus affecting the levels of protein in cells. Interestingly, a mechanism known as alternative polyadenylation (APA) enables mRNAs to escape miRNA regulation by generating mRNAs with 3'UTRs of different sizes. As many miRNA target sites are located within the 3'UTR, shortening the 3'UTR allows mRNAs to evade miRNAs targeting this region. The differences in the lengths and the sequence composition of the 3'UTRs may also impact the mRNA's translatability and subcellular localization. APA has been reported to regulate over 70% of protein coding genes, thus increasing the transcript repertoire. Several proteins, including mammalian cleavage factor, CFIm25 (NUDT21), have been shown to regulate APA. In this study we wanted to determine whether CFIm25 (NUDT21), itself a regulator of APA, undergoes APA to evade miRNA regulation. We used the blood cancer mantle cell lymphoma (MCL) cells as a model and showed that in these cells, NUDT21 is relatively stable with a long half-life. In addition, the NUDT21 pre-mRNA undergoes alternative APA within the same terminal exon. The three different sized NUDT21 mRNAs have different 3'UTR lengths and they each use a different canonical polyadenylation signal, AAUAAA, for 3'end cleavage and polyadenylation. Use of miRNA mimics and inhibitors showed that miR-23a, miR-222, and miR-323a play a significant role in regulating NUDT21 expression. Hence, these results suggest that NUDT21 mRNA is stable and the different 3'UTRs generated through APA of NUDT21 play an important role in evading miRNA regulation and offers insights into how levels of CFIm25 (NUDT21) may be fine-tuned as needed under different physiological and pathological conditions.
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