The RNA Transcript, August 8, 2022 |
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Wed, August 10, 2022
11:00 a.m. - 2:00 p.m.
1150 West Medical Center Drive
Driveway on the north side of the MSRBs
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Join the UMMS Office of Research for this event hosting dozens of exhibitors from labs and offices of the Medical School and across campus.
Researchpalooza is the perfect opportunity for colleagues and friends to have a great time and meet, mingle, and learn more about many of the organizations that offer their stellar services to faculty, students, and staff, all at one convenient time and location. Enter the Passport for Prizes to visit tables and win U-M swag!
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U-M Oral Dissertation Defense |
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Development of a Cell-Based Assay for the Detection of pre-miRNA-Protein Interactions
Monday, Aug 8, 2022
2:00 - 3:00 PM
Rackham East Conference Room
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U-M Oral Dissertation Defense |
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Modification and sequence of tRNAs and mRNAs impact translational speed and accuracy
Wednesday, Aug 10, 2022
9:00 - 10:00 AM
Rackham East Conference Room, 4th floor
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U-M Oral Dissertation Defense |
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Transcription Factor Interactions Governing Gene Regulation by the Wnt Signalling Pathway
Wednesday, Aug 10, 2022
11:00 - 12:00 PM
1010 Biological Sciences Building
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Wednesday, August 10, 2022
4:00 - 5:00 PM
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From ribosome biogenesis to gene expression regulation: small nucleolar RNAs (snoRNAs) target a wide transcriptome
RNA Mango aptamer tools: RNA imaging, sensors and RNA-protein complex pulldowns
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U-M Oral Dissertation Defense |
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Biochemical and Structural Characterization of the Starter Module in Saxitoxin Biosynthesis Pathway
Wednesday, Aug 17, 2022
10:00 - 11:00 AM
Life Sciences Institute
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Our members' publications are available through Altmetrics. Queries are currently available: CRISPR, microRNA, molecule, RNA, RNA therapeutics, transcriptome, and translation. Below are recent highlights.
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Slusher, A. L., Kim, J. J., Ribick, M., Pollens-Voigt, J., Bankhead, A., Palmbos, P. L., & Ludlow, A. T. (2022). Intronic Cis-Element DR8 in hTERT Is Bound by Splicing Factor SF3B4 and Regulates hTERT Splicing in Non-Small Cell Lung Cancer. Molecular cancer research : MCR, OF1–OF15. Advance online publication. https://doi.org/10.1158/1541-7786.MCR-21-0058
Splicing of the hTERT gene to produce the full-length (FL) transcript is necessary for telomerase enzyme activity and telomere-dependent cellular immortality in the majority of human tumors, including non-small cell lung cancer (NSCLC) cells. The molecular machinery to splice hTERT to the FL isoform remains mostly unknown. Previously, we reported that an intron 8 cis-element termed "direct repeat 8" (DR8) promotes FL hTERT splicing, telomerase, and telomere length maintenance when bound by NOVA1 and PTBP1 in NSCLC cells. However, some NSCLC cells and patient tumor samples lack NOVA1 expression. This leaves a gap in knowledge about the splicing factors and cis-elements that promote telomerase in the NOVA1-negative context. We report that DR8 regulates FL hTERT splicing in the NOVA1-negative and -positive lung cancer contexts. We identified splicing factor 3b subunit 4 (SF3B4) as an RNA trans-factor whose expression is increased in lung adenocarcinoma (LUAD) tumors compared with adjacent normal tissue and predicts poor LUAD patient survival. In contrast to normal lung epithelial cells, which continued to grow with partial reductions of SF3B4 protein, SF3B4 knockdown reduced hTERT splicing, telomerase activity, telomere length, and cell growth in lung cancer cells. SF3B4 was also demonstrated to bind the DR8 region of hTERT pre-mRNA in both NOVA1-negative and -positive NSCLC cells. These findings provide evidence that DR8 is a critical binding hub for trans-factors to regulate FL hTERT splicing in NSCLC cells. These studies help define mechanisms of gene regulation important to the generation of telomerase activity during carcinogenesis.
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Slusher, A. L., Kim, J. J., Ribick, M., & Ludlow, A. T. (2022). Acute Exercise Regulates hTERT Gene Expression and Alternative Splicing in the hTERT-BAC Transgenic Mouse Model. Medicine and science in sports and exercise, 54(6), 931–943. https://doi.org/10.1249/MSS.0000000000002868
Introduction: Aerobic exercise maintains telomere length through increased human telomerase reverse transcriptase (hTERT) expression and telomerase enzyme activity. The impact of acute exercise on hTERT alternative splicing (AS) is unknown.
Results: Compared with Pre, FL hTERT increased at Post before decreasing during recovery in the gastrocnemius (48 and 72 h; P ≤ 0.001) and left ventricle (24 h; P = 0.004). The percentage of FL hTERT in the gastrocnemius also increased during recovery (1 and 72 h; P ≤ 0.017), whereas a decrease was observed in the left ventricle (1, 24, and 48 h; P ≤ 0.041). hTERT decreased in the brain (48 h), whereas FL hTERT percentage remained unaltered. SF3B4 protein expression decreased throughout recovery in the gastrocnemius and tended to be associated with FL hTERT (r = −0.348, P = 0.075) and –β in opposite directions (r = 0.345, P = 0.067).
Conclusions: Endurance exercise increased hTERT gene expression, and altered FL hTERT splicing in contractile tissues and may maintain telomere length necessary to improve the function and health of the organism.
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Palomar, V.M., Jaksich, S., Fujii, S., Kuciński, J. and Wierzbicki, A.T. (2022), High-resolution map of plastid-encoded RNA polymerase binding patterns demonstrates a major role of transcription in chloroplast gene expression. Plant J. https://doi.org/10.1111/tpj.15882
Plastids contain their own genomes, which are transcribed by two types of RNA polymerases. One of those enzymes is a bacterial-type, multi-subunit polymerase encoded by the plastid genome. The plastid-encoded RNA polymerase (PEP) is required for efficient expression of genes encoding proteins involved in photosynthesis. Despite the importance of PEP, its DNA binding locations have not been studied on the genome-wide scale at high resolution. We established a highly specific approach to detect the genome-wide pattern of PEP binding to chloroplast DNA using plastid chromatin immunoprecipitation–sequencing (ptChIP-seq). We found that in mature Arabidopsis thaliana chloroplasts, PEP has a complex DNA binding pattern with preferential association at genes encoding rRNA, tRNA, and a subset of photosynthetic proteins. Sigma factors SIG2 and SIG6 strongly impact PEP binding to a subset of tRNA genes and have more moderate effects on PEP binding throughout the rest of the genome. PEP binding is commonly enriched on gene promoters, around transcription start sites. Finally, the levels of PEP binding to DNA are correlated with levels of RNA accumulation, which demonstrates the impact of PEP on chloroplast gene expression.
Keywords: plastid, RNA polymerase, sigma factor, transcription
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