scholarly journals Expression of Alternatively Spliced Sodium Channel α-Subunit Genes

2004 ◽  
Vol 279 (44) ◽  
pp. 46234-46241 ◽  
Author(s):  
Christopher K. Raymond ◽  
John Castle ◽  
Philip Garrett-Engele ◽  
Christopher D. Armour ◽  
Zhengyan Kan ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Sodium Channel ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Genomic Sequence ◽  
Molecular Medicine ◽  
Primate Model ◽  
Α Subunit ◽  
Alternatively Spliced ◽  
Splicing Patterns

Molecular medicine requires the precise definition of drug targets, and tools are now in place to provide genome-wide information on the expression and alternative splicing patterns of any known gene. DNA microarrays were used to monitor transcript levels of the nine well-characterized α-subunit sodium channel genes across a broad range of tissues from cynomolgus monkey, a non-human primate model. Alternative splicing of human transcripts for a subset of the genes that are expressed in dorsal root ganglia, SCN8A (Nav1.6), SCN9A (Nav1.7), and SCN11A (Nav1.9) was characterized in detail. Genomic sequence analysis among gene family paralogs and between cross-species orthologs suggested specific alternative splicing events within transcripts of these genes, all of which were experimentally confirmed in human tissues. Quantitative PCR revealed that certain alternative splice events are uniquely expressed in dorsal root ganglia. In addition to characterization of human transcripts, alternatively spliced sodium channel transcripts were monitored in a rat model for neuropathic pain. Consistent down-regulation of all transcripts was observed, as well as significant changes in the splicing patterns of SCN8A and SCN9A.

scholarly journals Snord67 promotes lymph node metastasis and regulates U6-mediated alternative splicing in breast cancer

2020 ◽  
Author(s):  
Yvonne L. Chao ◽  
Yinzhou Zhu ◽  
Hannah J. Wiedner ◽  
Yi-Hsuan Tsai ◽  
Lily Wilkinson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Alternative Splicing ◽  
Subsequent Development ◽  
Distant Metastases ◽  
Housekeeping Genes ◽  
Small Nuclear Rna ◽  
Alternatively Spliced ◽  
Rapid Autopsy ◽  
Splicing Patterns

AbstractSmall nucleolar RNAs (snoRNAs) have long been considered “housekeeping genes”, important for ribosomal biogenesis and protein synthesis. However, there is increasing evidence that this largely ignored class of non-coding RNAs (ncRNAs) also have wide-ranging, non-canonical functions in diseases, including cancer. SnoRNAs have been shown to have both oncogenic and tumor suppressor roles, yet whether snoRNAs regulate metastasis is unknown. Here we show that expression of certain snoRNAs are enriched in lymph node (LN) metastases in a micro-surgical, immune-competent mouse model of breast cancer. We identify the snoRNA Snord67 as a key regulator of LN metastasis. Knockout of Snord67 resulted in significantly decreased LN tumor growth and subsequent development of distant metastases. This was associated with loss of targeted 2’-O-methylation on the small nuclear RNA U6, a component of the spliceosome. RNA sequencing revealed distinct alternative splicing patterns in Snord67 knockout cells. Using rapid autopsy breast cancer cases, we found that matched human primary tumor and LN metastases revealed similar alternatively spliced genes, including several that are known to contribute to cancer. These results demonstrate that Snord67 is critical for growth of LN metastases and subsequent spread to distant metastases, and suggest that snoRNA-guided modifications of the spliceosome represent a previously unappreciated, yet targetable pathway in cancer.

scholarly journals Design and application of circular RNAs with protein-sponge function

2020 ◽  
Vol 48 (21) ◽  
pp. 12326-12335
Author(s):  
Silke Schreiner ◽  
Anna Didio ◽  
Lee-Hsueh Hung ◽  
Albrecht Bindereif
Keyword(s):  
Alternative Splicing ◽  
Mammalian Cells ◽  
Regulatory Networks ◽  
Rna Binding ◽  
Molecular Medicine ◽  
Circular Rnas ◽  
Ca Repeat ◽  
New Strategy ◽  
Nuclear Ribonucleoprotein ◽  
Splicing Patterns

Abstract Circular RNAs (circRNAs) are a class of noncoding RNAs, generated from pre-mRNAs by circular splicing of exons and functionally largely uncharacterized. Here we report on the design, expression, and characterization of artificial circRNAs that act as protein sponges, specifically binding and functionally inactivating hnRNP (heterogeneous nuclear ribonucleoprotein) L. HnRNP L regulates alternative splicing, depending on short CA-rich RNA elements. We demonstrate that designer hnRNP L-sponge circRNAs with CA-repeat or CA-rich sequence clusters can efficiently and specifically modulate splicing-regulatory networks in mammalian cells, including alternative splicing patterns and the cellular distribution of a splicing factor. This new strategy can in principle be applied to any RNA-binding protein, opening up new therapeutic strategies in molecular medicine.

Non-uniform expression of α subunit isoforms of the Na+/K+ pump in rat dorsal root ganglia neurons

1999 ◽  
Vol 821 (1) ◽  
pp. 212-217 ◽  
Author(s):  
Maxim Dobretsov ◽  
Stephanie L. Hastings ◽  
Joseph R. Stimers
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Α Subunit ◽  
Subunit Isoforms ◽  
Dorsal Root Ganglia Neurons

scholarly journals Functional Analysis of a Voltage-Gated Sodium Channel and Its Splice Variant from Rat Dorsal Root Ganglia

2002 ◽  
Vol 70 (6) ◽  
pp. 2262-2272 ◽  
Author(s):  
Paul S. Dietrich ◽  
Joseph G. McGivern ◽  
Stephen G. Delgado ◽  
Bruce D. Koch ◽  
Richard M. Eglen ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Sodium Channel ◽  
Dorsal Root Ganglia ◽  
Splice Variant ◽  
Dorsal Root ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated

Sodium channel Nav1.6 is up-regulated in the dorsal root ganglia in a mouse model of type 2 diabetes

2012 ◽  
Vol 87 (2-3) ◽  
pp. 244-249 ◽  
Author(s):  
Yan-Shun Ren ◽  
Nian-Song Qian ◽  
Yu Tang ◽  
Yong-Hui Liao ◽  
Yan-Ling Yang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Sodium Channel ◽  
Dorsal Root Ganglia ◽  
Dorsal Root

scholarly journals An oral form of methylglyoxal-bis-guanylhydrazone reduces monocyte activation and traffic to the dorsal root ganglia in a primate model of HIV-peripheral neuropathy

2017 ◽  
Vol 23 (4) ◽  
pp. 568-576 ◽  
Author(s):  
Jessica R. Lakritz ◽  
Samshita Yalamanchili ◽  
Michael J. Polydefkis ◽  
Andrew D. Miller ◽  
Michael S. McGrath ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Monocyte Activation ◽  
Primate Model ◽  
Oral Form

scholarly journals Article Commentary: The Alternatively Spliced Form “b” of the Epithelial Sodium Channel α subunit (α ENaC): Any Prior Evidence of its Existence?

2010 ◽  
Vol 4 ◽  
pp. CMC.S5270
Author(s):  
Marlene F. Shehata
Keyword(s):  
Sodium Channel ◽  
Mrna Expression ◽  
Epithelial Sodium Channel ◽  
Protein Band ◽  
Sodium Balance ◽  
Kidney Cortex ◽  
Western Blots ◽  
Α Subunit ◽  
Alternatively Spliced ◽  
Additional Protein

The epithelial sodium channel (ENaC) is critical in maintaining sodium balance across aldosterone-responsive epithelia. ENaC is a combined channel formed of three subunits (αβγ) with α ENaC subunit being the most critical for channel functionality. In a previous report, we have demonstrated the existence and mRNA expression levels of four alternatively spliced forms of the α ENaC subunit denoted by -a, -b, -c and -d in kidney cortex of Dahl S and R rats. Of the four alternatively spliced forms presently identified, α ENaC-b is considered the most interesting for the following reasons: Aside from being a salt-sensitive transcript, α ENaC-b mRNA expression is ~32 fold higher than α ENaC wildtype in kidney cortex of Dahl rats. Additionally, the splice site used to generate α ENaC-b is conserved across species. Finally, α ENaC-b mRNA expression is significantly higher in salt-resistant Dahl R rats versus salt-sensitive Dahl S rats. As such, this commentary aims to highlight some of the previously published research articles that described the existence of an additional protein band on α ENaC western blots that could account for α ENaC-b in other rat species.

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