A5091578429- MicroRNA in disease regulation
- RNA Research and Splicing
- RNA modifications and cancer
- RNA regulation and disease
- Circular RNAs in diseases
- Mitochondrial Function and Pathology
- Extracellular vesicles in disease
- RNA and protein synthesis mechanisms
- Autophagy in Disease and Therapy
- RNA Interference and Gene Delivery
- Animal Virus Infections Studies
- Cancer-related molecular mechanisms research
Queen's University Belfast
2023-2024
Indian Institute of Chemical Biology
2020-2022
Council of Scientific and Industrial Research
2020
microRNAs are short regulatory RNAs in metazoan cells. Regulation of miRNA activity and abundance is evident human cells where availability target messages can influence biogenesis by augmenting the Dicer1-dependent processing precursors to mature microRNAs. Requirement subcellular compartmentalization Ago2, key component repression machineries, for controlled miRNPs reported here. The process predominantly happens on polysomes attached with endoplasmic reticulum which Ago2 trafficking found...
Mitochondria, the "powerhouse" of mammalian cells, also serve as key storage sites for ions, metabolites, and enzymes vital metabolic regulation. Our data suggests a de novo role mitochondria miRNA sinks in cells. miR-122 is hepatic regulating processes liver. In this study, we observed increased mitochondrial targeting amino acid-starved Interestingly, when cells were refed with acids, gets relocalized reused cytosol translational repression process. Mitochondrial miRNAs (mito-miRs) follow...
Summary Decelerated translation elongation caused by non-optimal codons can reduce mRNA stability through codon optimality-mediated degradation . A key element of this process is the coupling sensing usage with regulation efficiency and stability. We report that two paralog RNA-binding proteins (ZC3H7A ZC3H7B), which are only found in Chordates, preferentially bind to mRNAs enriched A/U at their wobble sites (A/U3 codons). ZC3H7A/B engage ribosomes lack factors induce or block initiation...
Viruses use microRNAs (miRNAs) to impair the host antiviral response and facilitate viral infection by expressing their own miRNAs or co-opting cellular miRNAs. inhibit translation initiation of target mRNAs recruiting GIGYF2-4EHP (or EIF4E2) repressor complex mRNA 5'-cap structure. We recently reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-encoded non-structural protein (NSP2) interacts with GIGYF2. This interaction is critical for blocking Ifnb1 encodes cytokine...
Ribosome quality control (RQC) resolves collided ribosomes, thus preventing their cytotoxic effects. The chemotherapeutic agent 5-Fluorouracil (5FU) is best known for its misincorporation into DNA and inhibition of thymidylate synthase. However, while a major determinant 5FU's anticancer activity RNAs, the mechanisms by which cancer cells overcome RNA-dependent 5FU toxicity remain ill-defined. Here, we report role RQC in mitigating effects 5FU. We show that treatment results rapid induction...
MicroRNAs (miRNAs) are small regulatory RNAs of relatively long half-life in non-proliferative human cells. However, cancer cells the half-lives miRNAs comparatively short. To understand mechanism rapid miRNA turnover cells, we explored effect target mRNAs on abundance that repress them. We have noted an accelerated extracellular vesicle (EV)-mediated export presence their mammalian and this target-driven miRNA-export process is retarded by Ago2-interacting protein GW182B. The GW182 group...
Abstract Translation of aberrant or damaged mRNAs results in ribosome stalling and collisions. The Ribosome Quality Control (RQC) mechanism detects collided ribosomes removes nascent peptides, thus preventing their cytotoxic effects. Conversely, excessive unresolved collisions can induce apoptosis. 5-Fluorouracil (5FU) forms the backbone standard-of-care chemotherapeutic regimens for several types cancer. Although best known its incorporation into DNA inhibition thymidylate synthase, a major...
Abstract microRNAs (miRNAs) inhibit mRNA translation initiation by recruiting the GIGYF2/4EHP repressor complex to 5’ cap structure. Viruses utilise miRNAs impair host antiviral immune system and facilitate viral infection expressing their own or co-opting cellular miRNAs. We recently reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encoded non-structural protein (NSP2) interacts with GIGYF2. This interaction is critical for blocking of Ifn1-b encodes cytokine...
MicroRNAs (miRNAs) repress protein expression by binding to the target mRNAs. Exploring whether of one miRNA can regulate abundance and activity other miRNAs, we noted coordinated biogenesis miRNAs in activated macrophages. with higher numbers sites (the "primary" miRNAs) induce ("secondary" having on 3' untranslated region (UTR) common miR-146a-5p, macrophages, acts as a that coordinates "secondary" miR-125b, miR-21, or miR-142-3p new sets mRNAs balance immune responses. During biogenesis,...
Defective intracellular trafficking and export of microRNAs (miRNAs) have been observed in growth-retarded mammalian cells having impaired mitochondrial potential dynamics. Here, we found that uncoupling protein 2 (Ucp2)-mediated depolarization membrane also results progressive sequestration miRNAs within polysomes lowers their release via extracellular vesicles. Interestingly, the miRNA-trafficking process human could be reversed presence Genipin, an inhibitor Ucp2. Mitochondrial...
Abstract MicroRNAs (miRNAs) repress protein expression by binding to the 3’ UTR of target mRNAs. By exploring effect mRNA on biogenesis cognate miRNAs, we have noted miRNA with higher number sites (primary miRNA) coordinates and activity another (secondary having a common mRNA. From quantitative data obtained from macrophage cells, detected miR-146a-5p as “primary” that “secondary” miR-125b, miR-21 or miR-142-3p new sets mRNAs balance immune response in activated cells. Interestingly,...
Abstract Defective intracellular trafficking and export of miRNAs has been observed in senescent mammalian cells having impaired mitochondrial potential. Similar to what happens cells, Uncoupling Protein 2 mediated depolarization membrane potential results progressive sequestration with polysomes lowered release through extracellular vesicles. Supporting importance on miRNAs’ fate determination, miRNA-trafficking process growth retarded human found be reversed presence Genipin an inhibitor...