Transcriptional regulation of the human Raver2 ribonucleoprotein gene

Romanelli, Maria; Lorenzi, Pamela; Diani, Erica; Filippello, Agnese; Avesani, Francesca; Morandi, Carlo

doi:10.1016/j.gene.2011.11.036

Cited by 7 publications

(9 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The FANTOM5 promoter-based expression atlas ( 25 ) indicates that human RAVER2 , although ubiquitous ( 18 , 26 ), is highly expressed in the nervous system (Table 3 ), consistent with its dysregulation playing a role in ADLD pathogenesis. Together, these results support the view that lamin B1 levels modulate RAVER2 expression and that this regulation occurs in the mammalian central nervous system (CNS), the target organ of ADLD in humans.…”

Section: Resultsmentioning

confidence: 86%

Messenger RNA processing is altered in autosomal dominant leukodystrophy

Bartoletti-Stella

Gasparini

Giacomini

et al. 2015

Human Molecular Genetics

View full text Add to dashboard Cite

Adult-onset autosomal dominant leukodystrophy (ADLD) is a slowly progressive neurological disorder characterized by autonomic dysfunction, followed by cerebellar and pyramidal features. ADLD is caused by duplication of the lamin B1 gene (LMNB1), which leads to its increased expression. The molecular pathways involved in the disease are still poorly understood. Hence, we analyzed global gene expression in fibroblasts and whole blood of LMNB1 duplication carriers and used Gene Set Enrichment Analysis to explore their gene signatures. We found that LMNB1 duplication is associated with dysregulation of genes involved in the immune system, neuronal and skeletal development. Genes with an altered transcriptional profile clustered in specific genomic regions. Among the dysregulated genes, we further studied the role of RAVER2, which we found to be overexpressed at mRNA and protein level. RAVER2 encodes a putative trans regulator of the splicing repressor polypyrimidine tract binding protein (PTB) and is likely implicated in alternative splicing regulation. Functional studies demonstrated an abnormal splicing pattern of several PTB-target genes and of the myelin protein gene PLP1, previously demonstrated to be involved in ADLD. Mutant mice with different lamin B1 expression levels confirmed that Raver2 expression is dependent on lamin B1 in neural tissue and determines an altered splicing pattern of PTB-target genes and Plp1. Overall our results demonstrate that deregulation of lamin B1 expression induces modified splicing of several genes, likely driven by raver-2 overexpression, and suggest that an alteration of mRNA processing could be a pathogenic mechanism in ADLD.

show abstract

Section: Resultsmentioning

confidence: 86%

Messenger RNA processing is altered in autosomal dominant leukodystrophy

Bartoletti-Stella

Gasparini

Giacomini

et al. 2015

Human Molecular Genetics

View full text Add to dashboard Cite

show abstract

“…Human RBM20 transcript expression analyses were performed by PCR on Multiple Tissue cDNA panels (MTC™ panel I and II, BD Biosciences Clontech) representative for adult human tissues [6]. The MTC TM panel I and II consist of first‐strand cDNAs generated using oligo‐dT primers derived from poly (A) + RNA isolated from different human tissues.…”

Section: Methodsmentioning

confidence: 99%

Identification of nuclear retention domains in the RBM20 protein

Filippello¹,

Lorenzi²,

Bergamo³

et al. 2013

FEBS Letters

Self Cite

View full text Add to dashboard Cite

Edited by Ulrike KutayKeywords: RBM20 DCM Alternative splicing Nuclear localization Ribonucleoprotein SR a b s t r a c t RBM20 is a nuclear protein which regulates alternative splicing of expressed genes that have a key role in cardiac function. By cloning the human and mouse RBM20 cDNA, producing expressing vectors for truncated proteins, and comparing their sub-cellular distribution in transfected cells, we have identified the sequences necessary for RBM20 full nuclear retention. The region overlaps an RNA binding motif and a serine-arginine domain. The sequence is conserved in many species but belongs only to RBM20 orthologs. The RMB20 tissue specificity, together with the properties of its nuclear localization determinant, demonstrates a specific evolutionary selection of post-transcriptional regulation factors.

show abstract

“…Raver2 expression is restricted to differentiated neurons and glia cells. We have recently contributed to the characterization of Raver1 and Raver2 promoters and to the identification of cis -acting signals [62,67]. In contrast to Raver1, which binds to cytosolic proteins, so far there is no evidence of a Raver2 interaction with cytoplasmic proteins.…”

Section: Ptb Paralogs and Co-factorsmentioning

confidence: 99%

New Insights into Functional Roles of the Polypyrimidine Tract-Binding Protein

Romanelli

Diani

Lievens

2013

IJMS

Self Cite

114

View full text Add to dashboard Cite

Polypyrimidine Tract Binding Protein (PTB) is an intensely studied RNA binding protein involved in several post-transcriptional regulatory events of gene expression. Initially described as a pre-mRNA splicing regulator, PTB is now widely accepted as a multifunctional protein shuttling between nucleus and cytoplasm. Accordingly, PTB can interact with selected RNA targets, structural elements and proteins. There is increasing evidence that PTB and its paralog PTBP2 play a major role as repressors of alternatively spliced exons, whose transcription is tissue-regulated. In addition to alternative splicing, PTB is involved in almost all steps of mRNA metabolism, including polyadenylation, mRNA stability and initiation of protein translation. Furthermore, it is well established that PTB recruitment in internal ribosome entry site (IRES) activates the translation of picornaviral and cellular proteins. Detailed studies of the structural properties of PTB have contributed to our understanding of the mechanism of RNA binding by RNA Recognition Motif (RRM) domains. In the present review, we will describe the structural properties of PTB, its paralogs and co-factors, the role in post-transcriptional regulation and actions in cell differentiation and pathogenesis. Defining the multifunctional roles of PTB will contribute to the understanding of key regulatory events in gene expression.

show abstract

Transcriptional regulation of the human Raver2 ribonucleoprotein gene

Cited by 7 publications

References 46 publications

Messenger RNA processing is altered in autosomal dominant leukodystrophy

Messenger RNA processing is altered in autosomal dominant leukodystrophy

Identification of nuclear retention domains in the RBM20 protein

New Insights into Functional Roles of the Polypyrimidine Tract-Binding Protein

Contact Info

Product

Resources

About