scholarly journals hnRNP A/B Proteins: An Encyclopedic Assessment of Their Roles in Homeostasis and Disease

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 712
Author(s):  
Patricia A. Thibault ◽  
Aravindhan Ganesan ◽  
Subha Kalyaanamoorthy ◽  
Joseph-Patrick W. E. Clarke ◽  
Hannah E. Salapa ◽  
...  
Keyword(s):  
Alternative Splice ◽  
Rna Metabolism ◽  
Protein Family ◽  
Hnrnp A1 ◽  
Cell Type ◽  
Cell Homeostasis ◽  
Splice Isoforms ◽  
Alternative Splice Isoforms ◽  
Functional Differences ◽  
Cell Type Specific

The hnRNP A/B family of proteins is canonically central to cellular RNA metabolism, but due to their highly conserved nature, the functional differences between hnRNP A1, A2/B1, A0, and A3 are often overlooked. In this review, we explore and identify the shared and disparate homeostatic and disease-related functions of the hnRNP A/B family proteins, highlighting areas where the proteins have not been clearly differentiated. Herein, we provide a comprehensive assembly of the literature on these proteins. We find that there are critical gaps in our grasp of A/B proteins’ alternative splice isoforms, structures, regulation, and tissue and cell-type-specific functions, and propose that future mechanistic research integrating multiple A/B proteins will significantly improve our understanding of how this essential protein family contributes to cell homeostasis and disease.

scholarly journals APPRIS: annotation of principal and alternative splice isoforms

2012 ◽  
Vol 41 (D1) ◽  
pp. D110-D117 ◽  
Author(s):  
Jose Manuel Rodriguez ◽  
Paolo Maietta ◽  
Iakes Ezkurdia ◽  
Alessandro Pietrelli ◽  
Jan-Jaap Wesselink ◽  
...  
Keyword(s):  
Alternative Splice ◽  
Splice Isoforms ◽  
Alternative Splice Isoforms

P2-114 Cell-type specific processing of the APP protein family in drosophila

2004 ◽  
Vol 25 ◽  
pp. S257
Author(s):  
Alexander Loewer ◽  
Peter Soba ◽  
Michaela V. Bilic ◽  
David Kuttenkeuler ◽  
Konrad Beyreuther ◽  
...  
Keyword(s):  
Protein Family ◽  
Cell Type ◽  
Cell Type Specific

scholarly journals Identification of Novel Alternative Splice Isoforms of Circulating Proteins in a Mouse Model of Human Pancreatic Cancer

2008 ◽  
Vol 69 (1) ◽  
pp. 300-309 ◽  
Author(s):  
Rajasree Menon ◽  
Qing Zhang ◽  
Yan Zhang ◽  
Damian Fermin ◽  
Nabeel Bardeesy ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Model ◽  
Alternative Splice ◽  
Human Pancreatic Cancer ◽  
Splice Isoforms ◽  
Alternative Splice Isoforms

scholarly journals Computer-Aided Discovery of Small Molecules Targeting the RNA Splicing Activity of hnRNP A1 in Castration-Resistant Prostate Cancer

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 763 ◽  
Author(s):  
Lavinia Carabet ◽  
Eric Leblanc ◽  
Nada Lallous ◽  
Helene Morin ◽  
Fariba Ghaidi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Alternative Splice ◽  
Small Molecule ◽  
Rna Binding ◽  
Critical Role ◽  
Hnrnp A1 ◽  
Castration Resistant Prostate Cancer ◽  
Splice Isoforms ◽  
Castration Resistant ◽  
Computer Aided

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is a versatile RNA-binding protein playing a critical role in alternative pre-mRNA splicing regulation in cancer. Emerging data have implicated hnRNP A1 as a central player in a splicing regulatory circuit involving its direct transcriptional control by c-Myc oncoprotein and the production of the constitutively active ligand-independent alternative splice variant of androgen receptor, AR-V7, which promotes castration-resistant prostate cancer (CRPC). As there is an urgent need for effective CRPC drugs, targeting hnRNP A1 could, therefore, serve a dual purpose of preventing AR-V7 generation as well as reducing c-Myc transcriptional output. Herein, we report compound VPC-80051 as the first small molecule inhibitor of hnRNP A1 splicing activity discovered to date by using a computer-aided drug discovery approach. The inhibitor was developed to target the RNA-binding domain (RBD) of hnRNP A1. Further experimental evaluation demonstrated that VPC-80051 interacts directly with hnRNP A1 RBD and reduces AR-V7 messenger levels in 22Rv1 CRPC cell line. This study lays the groundwork for future structure-based development of more potent and selective small molecule inhibitors of hnRNP A1–RNA interactions aimed at altering the production of cancer-specific alternative splice isoforms.

scholarly journals An alternative splicing switch shapes neurexin repertoires in principal neurons versus interneurons in the mouse hippocampus

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Thi-Minh Nguyen ◽  
Dietmar Schreiner ◽  
Le Xiao ◽  
Lisa Traunmüller ◽  
Caroline Bornmann ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Rna Binding ◽  
Network Activity ◽  
Cell Type ◽  
Splice Isoforms ◽  
Mouse Hippocampus ◽  
Specific Alternative ◽  
Cell Type Specific ◽  
Splice Isoform ◽  
Functional Features

The unique anatomical and functional features of principal and interneuron populations are critical for the appropriate function of neuronal circuits. Cell type-specific properties are encoded by selective gene expression programs that shape molecular repertoires and synaptic protein complexes. However, the nature of such programs, particularly for post-transcriptional regulation at the level of alternative splicing is only beginning to emerge. We here demonstrate that transcripts encoding the synaptic adhesion molecules neurexin-1,2,3 are commonly expressed in principal cells and interneurons of the mouse hippocampus but undergo highly differential, cell type-specific alternative splicing. Principal cell-specific neurexin splice isoforms depend on the RNA-binding protein Slm2. By contrast, most parvalbumin-positive (PV+) interneurons lack Slm2, express a different neurexin splice isoform and co-express the corresponding splice isoform-specific neurexin ligand Cbln4. Conditional ablation of Nrxn alternative splice insertions selectively in PV+ cells results in elevated hippocampal network activity and impairment in a learning task. Thus, PV-cell-specific alternative splicing of neurexins is critical for neuronal circuit function

scholarly journals Alternative splice isoforms of small conductance calcium-activated SK2 channels differ in molecular interactions and surface levels

Channels ◽  
2014 ◽  
Vol 8 (1) ◽  
pp. 62-75 ◽  
Author(s):  
Elizabeth Storer Scholl ◽  
Antonella Pirone ◽  
Daniel H Cox ◽  
R Keith Duncan ◽  
Michele H Jacob
Keyword(s):  
Alternative Splice ◽  
Molecular Interactions ◽  
Splice Isoforms ◽  
Alternative Splice Isoforms ◽  
Small Conductance
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