Article
Multidisciplinary Sciences
Siobhan S. Pattwell, Sonali Arora, Nicholas Nuechterlein, Michael Zager, Keith R. Loeb, Patrick J. Cimino, Nikolas C. Holland, Noemi Reche-Ley, Hamid Bolouri, Damian A. Almiron Bonnin, Frank Szulzewsky, Vaishnavi V. Phadnis, Tatsuya Ozawa, Michael J. Wagner, Michael C. Haffner, Junyue Cao, Jay Shendure, Eric C. Holland
Summary: This article highlights the previously unidentified role of the neurotrophin receptor splice variant TrkB.T1 in neurodevelopment, embryogenesis, transformation, and oncogenesis. TrkB.T1 is an important isoform in these processes and is expressed in both embryonic and adult tumors. The study also reveals its interaction with developmental and oncogenic signaling pathways, suggesting its potential to reshape our understanding of developmental systems and oncology.
Article
Multidisciplinary Sciences
Zhaotong Cong, Fulai Zhou, Chao Zhang, Xinyu Zou, Huibing Zhang, Yuzhe Wang, Qingtong Zhou, Xiaoqing Cai, Qiaofeng Liu, Jie Li, Lijun Shao, Chunyou Mao, Xi Wang, Jihong Wu, Tian Xia, Li-Hua Zhao, Hualiang Jiang, Yan Zhang, H. Eric Xu, Xi Cheng, Dehua Yang, Ming-Wei Wang
Summary: The study found that a splice variant (SV1) of the human growth hormone-releasing hormone receptor is capable of transducing biased signal, selectively coupling to beta-arrestins while the main receptor activates Gs. Differences at the receptor N terminus lead to distinct downstream signaling pathways for GHRHR and SV1, with GHRHR predominantly activating Gs and SV1 selectively coupling to beta-arrestins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Zhuo Wang, Chen Li, Jiuyang Ding, Yanning Li, Zhihua Zhou, Yanjun Huang, Xiaohan Wang, Haoliang Fan, Jian Huang, Yitong He, Jianwei Li, Jun Chen, Pingming Qiu
Summary: This study investigated the serotonergic pathway involved in MA-induced emotional disorders using a chronic MA administration mouse model. The findings suggest that abnormal regulation of 5-HT2CR in the basolateral amygdala may contribute to the manifestation of emotional disorder-like symptoms induced by chronic MA use, making it a promising clinical target for treatment.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Winston H. Cuddleston, Junhao Li, Xuanjia Fan, Alexey Kozenkov, Matthew Lalli, Shahrukh Khalique, Stella Dracheva, Eran A. Mukamel, Michael S. Breen
Summary: This study investigates RNA editing in different cell populations of the human prefrontal cortex and reveals selective and highly cell type-specific RNA editing in neurons. The findings provide insights into the functional roles of RNA editing in the brain and its implications for brain disorders.
NATURE COMMUNICATIONS
(2022)
Article
Agriculture, Dairy & Animal Science
Xian-feng Wu, Yuan Liu, Jin-shun Zhan, Qin-lou Huang, Wen-yang Li
Summary: This study revealed a novel splice transcript of the CPT1a gene in goats, which is predicted to result in the skipping of exons 6-19. The expression patterns of CPT1a and this novel splice variant, CPT1a-sv1, showed spatial differences and were involved in brain development. These findings provide insights into the function of the CPT1a gene and the molecular mechanism of alternative splicing in goats.
ANIMAL BIOTECHNOLOGY
(2022)
Article
Endocrinology & Metabolism
Perrin Guyer, David Arribas-Layton, Anthony Manganaro, Cate Speake, Sandra Lord, Decio L. Eizirik, Sally C. Kent, Roberto Mallone, Eddie A. James
Summary: A recent study discovered novel splice variant and secretory granule antigens within the HLA class I peptidome of human islets, and found that CD8(+) T cells from peripheral blood and human islets recognize these antigens. Through a systematic discovery process, the study identified novel CD4(+) T cell epitopes derived from these antigens. The study further demonstrated the contribution of unconventional antigens to the loss of tolerance in autoimmune diabetes.
Article
Oncology
Jiaqian Liang, Liyang Wang, Larysa Poluben, Mannan Nouri, Seiji Arai, Lisha Xie, Olga S. Voznesensky, Laura Cato, Xin Yuan, Joshua W. Russo, Henry W. Long, Myles Brown, Shaoyong Chen, Steven P. Balk
Summary: In castration-resistant prostate cancer (CRPC), the splice variant ARv7 can function independently of the full length ARfl, with both contributing independently to overall AR activity.
Article
Endocrinology & Metabolism
Perrin Guyer, David Arribas-Layton, Anthony Manganaro, Cate Speake, Sandra Lord, Decio L. Eizirik, Sally C. Kent, Roberto Mallone, Eddie A. James
Summary: A recent discovery identified novel splice variant and secretory granule antigens in human islets, which were recognized by CD8(+) T cells. This study aimed to identify CD4(+) T cell epitopes derived from these antigens and found 145 potential epitopes. The significant findings included T cells recognizing distinct epitopes derived from cyclin I splice variant, neuroendocrine convertase 2, and urocortin-3 at frequencies similar to an immunodominant proinsulin epitope, suggesting the contribution of unconventional antigens to autoimmune diabetes.
Article
Multidisciplinary Sciences
Manjul Rana, Jianrong Dong, Matthew J. Robertson, Cristian Coarfa, Nancy L. Weigel
Summary: This study found differences in transcription and splicing regulation between AR-V7 and AR in prostate cancer, leading to the generation of different gene products.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Leonidas Stamatatos, Julie Czartoski, Yu-Hsin Wan, Leah J. Homad, Vanessa Rubin, Hayley Glantz, Moni Neradilek, Emilie Seydoux, Madeleine F. Jennewein, Anna J. MacCamy, Junli Feng, Gregory Mize, Stephen C. De Rosa, Andres Finzi, Maria P. Lemos, Kristen W. Cohen, Zoe Moodie, M. Juliana McElrath, Andrew T. McGuire
Summary: The study found that vaccination of both previously infected individuals and those who were not infected resulted in increased neutralizing antibody titers, with previously infected individuals showing a greater boost in neutralizing titers. Vaccination of naive individuals also elicited cross-neutralizing responses, but at lower titers.
Article
Multidisciplinary Sciences
Mitchell G. Kluesner, Walker S. Lahr, Cara-Lin Lonetree, Branden A. Smeester, Patricia N. Claudio-Vazquez, Samuel P. Pitzen, Madison J. Vignes, Samantha C. Lee, Samuel P. Bingea, Aneesha A. Andrews, Beau R. Webber, Branden S. Moriarity, Xiaohong Qiu, Nicholas J. Slipek, Emily J. Pomeroy
Summary: The study introduces SpliceR as a tool for designing, ranking, and testing sgRNAs for efficient gene disruption in T cells by targeting splice sites or introducing stop codons. Targeting splice donors is the most reliable disruption method, followed by targeting splice acceptors, and CBE BE4 is generally more effective than ABE ABE7.10.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Trevor J. Gonzalez, Katherine E. Simon, Leo O. Blondel, Marco M. Fanous, Angela L. Roger, Maribel Santiago Maysonet, Garth W. Devlin, Timothy J. Smith, Daniel K. Oh, L. Patrick Havlik, Ruth M. Castellanos Rivera, Jorge A. Piedrahita, Mai K. ElMallah, Charles A. Gersbach, Aravind Asokan
Summary: Researchers have successfully generated a cross-species compatible AAV (ccAAVs) vector using a viral evolutionary approach, and discovered a highly potent new variant AAV.cc47. AAV.cc47 demonstrated enhanced transduction efficiency compared to AAV serotype 9 in mouse, pig, and non-human primate models, showing great potential for gene therapy. This study focuses on investigating cross-species delivery of AAV and provides new theoretical insights for translating gene therapy into clinical applications.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
Steven Erwood, Teija M. Bily, Jason Lequyer, Joyce Yan, Nitya Gulati, Reid A. Brewer, Liangchi Zhou, Laurence Pelletier, Evgueni A. Ivakine, Ronald D. Cohn
Summary: This study demonstrates the use of the CRISPR prime editing method for high-throughput variant classification and functional characterization. The results show that the method is efficient and accurate, and can be applied to other genes with appropriate cellular assays.
NATURE BIOTECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Kimberley D. Katleba, Paramita M. Ghosh, Maria Mudryj
Summary: Multiple studies have shown the importance of androgen receptor (AR) splice variants (SVs) in prostate cancer progression and their diagnostic utility. However, studies have found that AR-SVs are also expressed in non-prostatic malignancies and have diverse roles in tumorigenesis. AR-SVs also play a role in non-cancer pathologies.
Article
Oncology
Safiya Khurshid, Matias Montes, Daniel F. Comiskey, Brianne Shane, Eleftheria Matsa, Francesca Jung, Chelsea Brown, Hemant Kumar Bid, Ruoning Wang, Peter J. Houghton, Ryan Roberts, Frank Rigo, Dawn Chandler
Summary: This study shows that RMS patients express increased levels of IR-A compared to control tissues. The alternative splicing of IR adapts to produce more IR-A in response to hypoxic stress. Decreasing IR-A expression can impede the IGF-2 pathway and mitigate tumor growth.
NPJ PRECISION ONCOLOGY
(2022)