Molecular diversity in T-type Ca(2+) channels is produced by expression of three genes, and alternative splicing of those genes. Prompted by differences noted between rat and human Ca(v)3.3 sequences, we searched for splice variants. We cloned six variants, which are produced by splicing at exon 33 and exon 34. Expression of the variants differed between brain regions. The electrophysiological properties of the variants displayed similar voltage-dependent gating, but differed in their kinetic properties. The functional impact of splicing was inter-related, suggesting an interaction. We conclude that alternative splicing of the Ca(v)3.3 gene produces channels with distinct properties.
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http://dx.doi.org/10.1016/s0014-5793(02)03341-0 | DOI Listing |
Cells
December 2024
Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan.
Alternative splicing is essential for the generation of various protein isoforms that are involved in cell differentiation and tissue development. In addition to internal coding exons, alternative splicing affects the exons with translation initiation codons; however, little is known about these exons. Here, we performed a systematic classification of human alternative exons using coding information.
View Article and Find Full Text PDFGenes Cells
January 2025
Jiangsu Key Laboratory for Pathogens and Ecosystems, College of Life Sciences, Nanjing Normal University, Nanjing, China.
Serine-arginine protein kinases (SRPKs) play important roles in diverse biological processes such as alternative splicing and cell cycle. However, the functions of SRPKs in DNA damage response remain unclear. Here we characterized the function of SRPKs homolog Dsk1 in regulating DNA repair in the fission yeast Schizosaccharomyces pombe.
View Article and Find Full Text PDFOncogene
January 2025
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, USA.
Lung cancer is one of the most frequently diagnosed cancers in the US. African-American (AA) men are more likely to develop lung cancer with higher incidence and mortality rates than European-American (EA) men. Herein, we report high-confidence alternative splicing (AS) events from high-throughput, high-depth total RNA sequencing of lung tumors and non-tumor adjacent tissues (NATs) in two independent cohorts of patients with adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC).
View Article and Find Full Text PDFNat Commun
January 2025
Division of Genome Analysis Platform Development, National Cancer Center Research Institute, Tokyo, Japan.
Genomic variants causing abnormal splicing play important roles in genetic disorders and cancer development. Among them, variants that cause the formation of novel splice-sites (splice-site creating variants, SSCVs) are particularly difficult to identify and often overlooked in genomic studies. Additionally, these SSCVs are frequently considered promising candidates for treatment with splice-switching antisense oligonucleotides (ASOs).
View Article and Find Full Text PDFJ Med Genet
January 2025
Univ Rouen Normandie, Inserm U1245, Normandie Univ, CHU Rouen, Department of Genetics, F-76000, Rouen, France
Background: Li-Fraumeni syndrome (LFS) predisposes individuals to a wide range of cancers from childhood onwards, underscoring the crucial need for accurate interpretation of germline variants for optimal clinical management of patients and families. Several unclassified variants, particularly those potentially affecting splicing, require specialised testing. One such example is the NM_000546.
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