scholarly journals The X-linked splicing regulator MBNL3 has been co-opted to restrict placental growth in eutherians

2021 ◽  
Author(s):  
Thomas Spruce ◽  
Mireya Plass ◽  
André Gohr ◽  
Debashish Ray ◽  
María Martínez de Lagrán ◽  
...  
Keyword(s):  
Resource Allocation ◽  
Cellular Differentiation ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Sequence Evolution ◽  
Biological Functions ◽  
Double Knockout ◽  
Major Site ◽  
Genetic Conflict ◽  
Splicing Regulator

AbstractThe eutherian placenta is a major site for parental genetic conflict. Here, we identify the X-linked Mbnl3 gene as a novel player in this dispute. Mbnl3 belongs to an RNA binding protein family whose members regulate alternative splicing and other aspects of RNA metabolism in association with cellular differentiation. We find that, in eutherians, Mbnl3 has become specifically expressed in placenta and has undergone accelerated sequence evolution leading to changes in its RNA binding specificities. Although its molecular roles are partly redundant with those of Mbnl2, Mbnl3 has also acquired novel biological functions. In particular, whereas Mbnl2;Mbnl3 double knockout mice display severe placental maturation defects leading to strong histological and functional abnormalities, Mbnl3 knockout alone results in increased placental growth and favors placental and fetal resource allocation during limiting conditions.

The RNA-Binding Protein TIA-1 Is a Novel Mammalian Splicing Regulator Acting through Intron Sequences Adjacent to a 5′ Splice Site

2000 ◽  
Vol 20 (17) ◽  
pp. 6287-6299 ◽  
Author(s):  
Fabienne Del Gatto-Konczak ◽  
Cyril F. Bourgeois ◽  
Caroline Le Guiner ◽  
Liliane Kister ◽  
Marie-Claude Gesnel ◽  
...  
Keyword(s):  
Splice Site ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Splicing Regulator

scholarly journals The RNA-Binding Protein TIA-1 Is a Novel Mammalian Splicing Regulator Acting through Intron Sequences Adjacent to a 5′ Splice Site

2000 ◽  
Vol 20 (17) ◽  
pp. 6287-6299 ◽  
Author(s):  
Fabienne Del Gatto-Konczak ◽  
Cyril F. Bourgeois ◽  
Caroline Le Guiner ◽  
Liliane Kister ◽  
Marie-Claude Gesnel ◽  
...  
Keyword(s):  
Splice Site ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Dependent Manner ◽  
Splice Sites ◽  
Protein Fusion ◽  
Cell Extracts ◽  
U1 Snrnp ◽  
Splicing Regulator

ABSTRACT Splicing of the K-SAM alternative exon of the fibroblast growth factor receptor 2 gene is heavily dependent on the U-rich sequence IAS1 lying immediately downstream from its 5′ splice site. We show that IAS1 can activate the use of several heterologous 5′ splice sites in vitro. Addition of the RNA-binding protein TIA-1 to splicing extracts preferentially enhances the use of 5′ splice sites linked to IAS1. TIA-1 can provoke a switch to use of such sites on pre-mRNAs with competing 5′ splice sites, only one of which is adjacent to IAS1. Using a combination of UV cross-linking and specific immunoprecipitation steps, we show that TIA-1 binds to IAS1 in cell extracts. This binding is stronger if IAS1 is adjacent to a 5′ splice site and is U1 snRNP dependent. Overexpression of TIA-1 in cultured cells activates K-SAM exon splicing in an IAS1-dependent manner. If IAS1 is replaced with a bacteriophage MS2 operator, splicing of the K-SAM exon can no longer be activated by TIA-1. Splicing can, however, be activated by a TIA-1–MS2 coat protein fusion, provided that the operator is close to the 5′ splice site. Our results identify TIA-1 as a novel splicing regulator, which acts by binding to intron sequences immediately downstream from a 5′ splice site in a U1 snRNP-dependent fashion. TIA-1 is distantly related to the yeast U1 snRNP protein Nam8p, and the functional similarities between the two proteins are discussed.

scholarly journals The p53-induced RNA-binding protein ZMAT3 is a splicing regulator that inhibits the splicing of oncogenic CD44 variants in colorectal carcinoma

2020 ◽  
Vol 35 (1-2) ◽  
pp. 102-116
Author(s):  
Bruna R. Muys ◽  
Dimitrios G. Anastasakis ◽  
Duncan Claypool ◽  
Lörinc Pongor ◽  
Xiao Ling Li ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Splicing Regulator

scholarly journals C. elegans LIN-28 controls temporal cell-fate progression by regulating LIN-46 expression via the 5’UTR of lin-46 mRNA

2019 ◽  
Author(s):  
Orkan Ilbay ◽  
Charles Nelson ◽  
Victor Ambros
Keyword(s):  
Cell Fate ◽  
Cellular Differentiation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Cell Types ◽  
Cell Fates ◽  
C Elegans ◽  
L1 And L2 ◽  
Proliferative Cell

ABSTRACTHuman Lin28 is a conserved RNA-binding protein that promotes proliferation and pluripotency and can be oncogenic. Lin28 and C. elegans LIN-28 bind to precursor RNAs of the conserved, cellular differentiation-promoting, microRNA let-7 and inhibits production of mature let-7 microRNA. Lin28/LIN-28 also binds to and regulates many mRNAs in various cell types. However, the determinants and consequences of these LIN-28-mRNA interactions are not well understood. Here, we report that LIN-28 in C. elegans represses the expression of LIN-46, a downstream protein in the heterochronic pathway, via the 5’ UTR of the lin-46 mRNA. We show that both LIN-28 and the 5’UTR of lin-46 are required to prevent LIN-46 expression in the L1 and L2 stages, and that precocious LIN-46 expression is sufficient to skip L2 stage proliferative cell-fates, resulting in heterochronic defects similar to the ones observed in lin-28(0) animals. We propose that the lin-46 5’UTR mediates LIN-28 binding to and repression of the lin-46 mRNA. Our results demonstrate that precocious LIN-46 expression alone can account for lin-28(0) phenotypes, demonstrating the biological importance of regulation of individual target mRNAs by LIN-28.

235: The RNA-Binding Protein IMP3: A Novel Molecular Marker Predicts Progression of Superficial (TA and T1) Urothelial Carcinomas of Bladder

2007 ◽  
Vol 177 (4S) ◽  
pp. 78-79
Author(s):  
Lioudmila Sitnikova ◽  
Gary Mendese ◽  
Qin Lui ◽  
Bruce A. Woda ◽  
Di Lu ◽  
...  
Keyword(s):  
Molecular Marker ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Urothelial Carcinomas
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