Browsing by Author "Jin, Hong"

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    Monoallelically expressed noncoding RNAs form nucleolar territories on NOR-containing chromosomes and regulate rRNA expression
    (eLife Sciences, 2024-01-19) Hao, Qinyu; Liu, Minxue; Daulatabad, Swapna Vidhur; Gaffari, Saba; Song, You Jin; Srivastava, Rajneesh; Bhaskar, Shivang; Moitra, Anurupa; Mangan, Hazel; Tseng, Elizabeth; Gilmore, Rachel B.; Frier, Susan M.; Chen, Xin; Wang, Chengliang; Huang, Sui; Chamberlain, Stormy; Jin, Hong; Korlach, Jonas; McStay, Brian; Sinha, Saurabh; Janga, Sarath Chandra; Prasanth, Supriya G.; Prasanth, Kannanganattu V.; Biomedical Engineering and Informatics, Luddy School of Informatics, Computing, and Engineering
    Out of the several hundred copies of rRNA genes arranged in the nucleolar organizing regions (NOR) of the five human acrocentric chromosomes, ~50% remain transcriptionally inactive. NOR-associated sequences and epigenetic modifications contribute to the differential expression of rRNAs. However, the mechanism(s) controlling the dosage of active versus inactive rRNA genes within each NOR in mammals is yet to be determined. We have discovered a family of ncRNAs, SNULs (Single NUcleolus Localized RNA), which form constrained sub-nucleolar territories on individual NORs and influence rRNA expression. Individual members of the SNULs monoallelically associate with specific NOR-containing chromosomes. SNULs share sequence similarity to pre-rRNA and localize in the sub-nucleolar compartment with pre-rRNA. Finally, SNULs control rRNA expression by influencing pre-rRNA sorting to the DFC compartment and pre-rRNA processing. Our study discovered a novel class of ncRNAs influencing rRNA expression by forming constrained nucleolar territories on individual NORs.
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    Targeting long non-coding RNA NUDT6 enhances smooth muscle cell survival and limits vascular disease progression
    (Cold Spring Harbor Laboratory, 2023-06-07) Winter, Hanna; Winski, Greg; Busch, Albert; Chernogubova, Ekaterina; Fasolo, Francesca; Wu, Zhiyuan; Bäcklund, Alexandra; Khomtchouk, Bohdan B.; Van Booven, Derek J.; Sachs, Nadja; Eckstein, Hans-Henning; Wittig, Ilka; Boon, Reinier A.; Jin, Hong; Maegdefessel, Lars; Biohealth Informatics, School of Informatics and Computing
    Long non-coding RNAs (lncRNAs) orchestrate various biological processes and regulate the development of cardiovascular diseases. Their potential therapeutic benefit to tackle disease progression has recently been extensively explored. Our study investigates the role of lncRNA Nudix Hydrolase 6 (NUDT6) and its antisense target fibroblast growth factor 2 (FGF2) in two vascular pathologies: abdominal aortic aneurysms (AAA) and carotid artery disease. Using tissue samples from both diseases, we detected a substantial increase of NUDT6, whereas FGF2 was downregulated. Targeting Nudt6 in vivo with antisense oligonucleotides in three murine and one porcine animal model of carotid artery disease and AAA limited disease progression. Restoration of FGF2 upon Nudt6 knockdown improved vessel wall morphology and fibrous cap stability. Overexpression of NUDT6 in vitro impaired smooth muscle cell (SMC) migration, while limiting their proliferation and augmenting apoptosis. By employing RNA pulldown followed by mass spectrometry as well as RNA immunoprecipitation, we identified Cysteine and Glycine Rich Protein 1 (CSRP1) as another direct NUDT6 interaction partner, regulating cell motility and SMC differentiation. Overall, the present study identifies NUDT6 as a well-conserved antisense transcript of FGF2. NUDT6 silencing triggers SMC survival and migration and could serve as a novel RNA-based therapeutic strategy in vascular diseases.