scholarly journals Alternative splicing of the neurofibromatosis type I pre-mRNA

2011 ◽  
Vol 32 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Victoria A. Barron ◽  
Hua Lou
Keyword(s):  
Alternative Splicing ◽  
T Cell ◽  
Rna Binding ◽  
Binding Protein ◽  
Phenotypic Expression ◽  
Neurofibromatosis Type ◽  
Type I ◽  
Neurofibromatosis Type I ◽  
Variable Expression ◽  
Intracellular Antigen

NF1 (neurofibromatosis type I) is a common genetic disease that affects one in 3500 individuals. The disease is completely penetrant but shows variable phenotypic expression in patients. NF1 is a large gene, and its pre-mRNA undergoes alternative splicing. The NF1 protein, neurofibromin, is involved in diverse signalling cascades. One of the best characterized functions of NF1 is its function as a Ras-GAP (GTPase-activating protein). NF1 exon 23a is an alternative exon that lies within the GAP-related domain of neurofibromin. This exon is predominantly included in most tissues, and it is skipped in CNS (central nervous system) neurons. The isoform in which exon 23a is skipped has 10 times higher Ras-GAP activity than the isoform in which exon 23a is included. Exon 23a inclusion is tightly regulated by at least three different families of RNA-binding proteins: CELF {CUG-BP (cytosine-uridine-guanine-binding protein) and ETR-3 [ELAV (embryonic lethal abnormal vision)-type RNA-binding protein]-like factor}, Hu and TIA-1 (T-cell intracellular antigen 1)/TIAR (T-cell intracellular antigen 1-related protein). The CELF and Hu proteins promote exon 23a skipping, while the TIA-1/TIAR proteins promote its inclusion. The widespread clinical variability that is observed among NF1 patients cannot be explained by NF1 mutations alone and it is believed that modifier genes may have a role in the variability. We suggest that the regulation of alternative splicing may act as a modifier to contribute to the variable expression in NF1 patients.

scholarly journals The RNA-binding protein hnRNPLL induces a T cell alternative splicing program delineated by differential intron retention in polyadenylated RNA

2014 ◽  
Vol 15 (1) ◽  
pp. R26 ◽  
Author(s):  
Vicky Cho ◽  
Yan Mei ◽  
Arleen Sanny ◽  
Stephanie Chan ◽  
Anselm Enders ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
T Cell ◽  
Rna Binding ◽  
Binding Protein ◽  
Intron Retention ◽  
Rna Binding Protein ◽  
Polyadenylated Rna

scholarly journals The RNA-Binding Protein KSRP Modulates Cytokine Expression of CD4+ T Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Rudolf Käfer ◽  
Lisa Schmidtke ◽  
Katharina Schrick ◽  
Evelyn Montermann ◽  
Matthias Bros ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Cytokine Expression ◽  
Negative Regulator ◽  
Control Group ◽  
Type I

The KH-type splicing regulatory protein (KSRP) is a RNA-binding protein, which regulates the stability of many mRNAs encoding immune-relevant proteins. As KSRP regulates innate immune responses, for instance by the modulation of type I interferon mRNA stability, we were interested whether knockdown of the protein (KSRP-/-) interferes with T cell activation and polarization. Polyclonally stimulated KSRP-/- CD4+ T cells proliferated at a higher extent and higher frequency and expressed the activation marker CD25 more than wild-type T cells. In supernatants of stimulated KSRP-/- CD4+ T cells, levels of IL-5, IL-9, IL-10, and IL-13 were observed to be increased compared to those of the control group. KSRP-/- CD8+ T cells showed no altered proliferative capacity upon polyclonal stimulation, but supernatants contained lower levels of interferon-γ. Similar changes in the cytokine expression patterns were also detected in T cells derived from KSRP-/- mice undergoing arthritis induction indicative of a pathophysiological role of KSRP-dependent T cell polarization. We demonstrated the direct binding of KSRP to the 3′ untranslated region of IL-13, IL-10, and IFN-γ mRNA in in vitro experiments. Moreover, since IL-4 mRNA decay was reduced in KSRP-/- CD4+ T cells, we identify KSRP as a negative regulator of IL-4 expression. These data indicate that overexpression of IL-4, which constitutes the primary inducer of Th2 polarization, may cause the Th2 bias of polyclonally stimulated KSRP-/- CD4+ T cells. This is the first report demonstrating that KSRP is involved in the regulation of T cell responses. We present strong evidence that T cells derived from KSRP-/- mice favor Th2-driven immune responses.

Can 18FDG-PET detect malignant transformation of neurofibromas in patients with neurofibromatosis type I?

2006 ◽  
Vol 37 (06) ◽  
Author(s):  
J Neinert ◽  
E Fastnacht ◽  
R Larisch ◽  
E Legius ◽  
R Engelskirchen ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Neurofibromatosis Type ◽  
Type I ◽  
Neurofibromatosis Type I ◽  
18Fdg Pet

scholarly journals The RNA-binding protein Sam68 modulates the alternative splicing of Bcl-x

2007 ◽  
Vol 176 (7) ◽  
pp. 929-939 ◽  
Author(s):  
Maria Paola Paronetto ◽  
Tilman Achsel ◽  
Autumn Massiello ◽  
Charles E. Chalfant ◽  
Claudio Sette
Keyword(s):  
Alternative Splicing ◽  
Tyrosine Phosphorylation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Live Cells ◽  
Hnrnp A1 ◽  
Splice Site Selection ◽  
Subnuclear Localization ◽  
Mrna Targets

The RNA-binding protein Sam68 is involved in apoptosis, but its cellular mRNA targets and its mechanism of action remain unknown. We demonstrate that Sam68 binds the mRNA for Bcl-x and affects its alternative splicing. Depletion of Sam68 by RNA interference caused accumulation of antiapoptotic Bcl-x(L), whereas its up-regulation increased the levels of proapoptotic Bcl-x(s). Tyrosine phosphorylation of Sam68 by Fyn inverted this effect and favored the Bcl-x(L) splice site selection. A point mutation in the RNA-binding domain of Sam68 influenced its splicing activity and subnuclear localization. Moreover, coexpression of ASF/SF2 with Sam68, or fusion with an RS domain, counteracted Sam68 splicing activity toward Bcl-x. Finally, Sam68 interacted with heterogenous nuclear RNP (hnRNP) A1, and depletion of hnRNP A1 or mutations that impair this interaction attenuated Bcl-x(s) splicing. Our results indicate that Sam68 plays a role in the regulation of Bcl-x alternative splicing and that tyrosine phosphorylation of Sam68 by Src-like kinases can switch its role from proapoptotic to antiapoptotic in live cells.

scholarly journals Folliculosebaceous Cystic Hamartoma in a Patient with Neurofibromatosis Type I

2011 ◽  
Vol 23 (Suppl 2) ◽  
pp. S185 ◽  
Author(s):  
Seongmin Noh ◽  
Ji Eun Kwon ◽  
Kwang Gil Lee ◽  
Mi Ryung Roh
Keyword(s):  
Neurofibromatosis Type ◽  
Type I ◽  
Neurofibromatosis Type I ◽  
Cystic Hamartoma
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