Alternative splicing of exons 29 and 30 in the neurofibromatosis type 1 gene

1998 ◽  
Vol 103 (4) ◽  
pp. 382-385 ◽  
Author(s):  
V. M. Park ◽  
Kathleen A. Kenwright ◽  
Dawn B. Sturtevant ◽  
Enikö Kármá Pivnick
Keyword(s):  
Alternative Splicing ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type

scholarly journals Neurofibromatosis type 1 alternative splicing is a key regulator of Ras/ERK signaling and learning behaviors in mice

2017 ◽  
Vol 26 (19) ◽  
pp. 3797-3807 ◽  
Author(s):  
Hieu T. Nguyen ◽  
Melissa N. Hinman ◽  
Xuan Guo ◽  
Alok Sharma ◽  
Hiroyuki Arakawa ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Erk Signaling ◽  
Learning Behaviors

Alternative splicing of neurofibromatosis type 1 gene transcript in malignant brain tumors: PCR analysis of frozen-section mRNA

1992 ◽  
Vol 6 (2) ◽  
pp. 83-87 ◽  
Author(s):  
Hiroshi Mochizuki ◽  
Toru Nishi ◽  
Janet M. Bruner ◽  
Polly S. Y. Lee ◽  
Victor A. Levin ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Brain Tumors ◽  
Neurofibromatosis Type 1 ◽  
Frozen Section ◽  
Neurofibromatosis Type ◽  
Pcr Analysis ◽  
Gene Transcript ◽  
Malignant Brain Tumors

scholarly journals Alternative Splicing of Neurofibromatosis Type 1 Exon 23a Modulates Ras/ERK Signaling and Learning Behaviors in Mice

2021 ◽  
Author(s):  
Karl Andreas Mader ◽  
Hua Lou
Keyword(s):  
Alternative Splicing ◽  
Neurofibromatosis Type 1 ◽  
Molecular Mechanisms ◽  
Neurofibromatosis Type ◽  
Gap Function ◽  
Erk Signaling ◽  
Learning Behaviors ◽  
Nf1 Gene

Neurofibromin is one of the few Ras-GTP activating proteins (Ras-GAPs) expressed in the brain. Disruption of its expression leads to the detrimental disease neurofibromatosis type 1 (NF1). Many studies have revealed the crucial role of NF1 in developing and adult tissues. However, these studies have focused on the expression of the entire NF1 gene and largely ignored the role of an alternative splicing event that controls the Ras-GAP function of neurofibromin. The focus of this chapter is NF1 exon 23a. This exon is located in the GAP-related domain (GRD) of neurofibromin. Its expression level, indicated by the percentage of its inclusion in the NF1 mRNA transcripts, has a profound effect on the Ras-GAP function of neurofibromin. In this chapter, we review the expression pattern of exon 23a and the molecular mechanisms that regulate its expression. We then discuss the role of its expression in Ras/ERK signaling and learning behaviors in mice. Lastly, we propose a few directions for future studies.

scholarly journals Regulation of Neuron-Specific Alternative Splicing of Neurofibromatosis Type 1 Pre-mRNA

2007 ◽  
Vol 28 (4) ◽  
pp. 1240-1251 ◽  
Author(s):  
Hui Zhu ◽  
Melissa N. Hinman ◽  
Robert A. Hasman ◽  
Priyesh Mehta ◽  
Hua Lou
Keyword(s):  
Alternative Splicing ◽  
Splice Site ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
Exon Definition ◽  
Nuclear Extracts ◽  
Hu Proteins ◽  
Novel Strategy

ABSTRACT Neurofibromatosis type 1 (NF1) is one of the most common heritable autosomal dominant disorders. Alternative splicing modulates the function of neurofibromin, the NF1 gene product, by inserting the in-frame exon 23a into the region of NF1 mRNA that encodes the GTPase-activating protein-related domain. This insertion, which is predominantly skipped in neurons, reduces the ability of neurofibromin to regulate Ras by 10-fold. Here, we report that the neuron-specific Hu proteins control the production of the short protein isoform by suppressing inclusion of NF1 exon 23a, while TIA-1/TIAR proteins promote inclusion of this exon. We identify two binding sites for Hu proteins, located upstream and downstream of the regulated exon, and provide biochemical evidence that Hu proteins specifically block exon definition by preventing binding of essential splicing factors. In vitro analyses using nuclear extracts show that at the downstream site, Hu proteins prevent binding of U1 and U6 snRNPs to the 5′ splice site, while TIAR increases binding. Hu proteins also decrease U2AF binding at the 3′ splice site located upstream of exon 23a. In addition to providing the first mechanistic insight into tissue-specific control of NF1 splicing, these studies establish a novel strategy whereby Hu proteins regulate RNA processing.

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