hnRNP Proteins and Splicing Control

Martínez-Contreras, Rebeca D.; Cloutier, Philippe; Shkreta, Lulzim; Fisette, Jean-François; Revil, Timothée; Chabot, Benoit

doi:10.1007/978-0-387-77374-2_8

Cited by 348 publications

(274 citation statements)

References 249 publications

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“…[15][16][17][18] An interesting switch in the abundance of the splicing regulator polypyrimidine tract binding protein (PTB) to its neuronal counterpart nPTB represents an important trigger in neuronal their interactors. 11,12 In general, binding sites for SR proteins are more frequent in true exons, and hnRNP binding sites are more often found in introns.…”

Section: The Importance Of Exon Definitionmentioning

confidence: 99%

Repair of pre-mRNA splicing

2010

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Section: The Importance Of Exon Definitionmentioning

confidence: 99%

Repair of pre-mRNA splicing

2010

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“…hnRNPs bind to RNA via RNA recognition motifs and influence diverse cellular events such as transcription; telomere maintenance; RNA splicing; polyadenylation; and mRNA localization, translation, and decay (26,27). hnRNPs are known to be negative splicing regulators by directly antagonizing the recognition of splice sites or interfering with the binding of splicing regulators to splicing enhancer sequences (28). More recently, Drosophila hnRNP M, HRP59, has been shown to bind to its own mRNA, inhibiting HRP59-mediated exon 3 inclusion (29,30).…”

Section: Discussionmentioning

confidence: 99%

Regulatory Roles of Heterogeneous Nuclear Ribonucleoprotein M and Nova-1 Protein in Alternative Splicing of Dopamine D2 Receptor Pre-mRNA

Park

Iaccarino

Lee

et al. 2011

Journal of Biological Chemistry

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The dopamine D2 receptor (D2R) plays a crucial role in the regulation of diverse key physiological functions, including motor control, reward, learning, and memory. This receptor is present in vivo in two isoforms, D2L and D2S, generated from the same gene by alternative pre-mRNA splicing. Each isoform has a specific role in vivo, underlining the importance of a strict control of its synthesis, yet the molecular mechanism modulating alternative D2R pre-mRNA splicing has not been completely elucidated. Here, we identify heterogeneous nuclear ribonucleoprotein M (hnRNP M) as a key molecule controlling D2R splicing. We show that binding of hnRNP M to exon 6 inhibited the inclusion of this exon in the mRNA. Importantly, the splicing factor Nova-1 counteracted hnRNP M effects on D2R premRNA splicing. Indeed, mutations of the putative Nova-1-binding site on exon 6 disrupted Nova-1 RNA assembly and diminished the inhibitory effect of Nova-1 on hnRNP M-dependent exon 6 exclusion. These results identify Nova-1 and hnRNP M as D2R pre-mRNA-binding proteins and show their antagonistic role in the alternative splicing of D2R pre-mRNA.Dopamine is a key regulator of mammalian central nervous system functions. Dysfunctions of the dopaminergic system are linked to neurological and neuropsychiatric disorders and to pituitary tumors (1). Dopamine action is mediated through activation of dopamine receptors. Among them, the dopamine D2 receptor (D2R) 4 is a major target of pharmacological interventions for the treatment of Parkinson disease, schizophrenia, depression, and pituitary tumors. The generation of D2R knock-out mice has highlighted its key role in the control of motor functions (2), regulation of reward circuitries (3, 4), and pituitary physiology (5, 6). D2R also acts as the main dopaminergic autoreceptor (7-9). Two isoforms of D2R, long (D2L) and short (D2S), are produced from the same gene by alternative pre-mRNA splicing (10). D2L differs from D2S by an additional 29 amino acids encoded by exon 6, inserted within the third cytoplasmic loop of the receptor, the region interacting with G proteins. This insertion likely accounts for a differential interaction of D2L and D2S with G proteins (11), activation of distinct downstream signaling pathways (6, 12), and function (12, 13). Indeed, analyses of D2L knock-out mice suggest that D2L is involved mainly in the control of postsynaptic functions, whereas D2S is involved in the control of dopamine neuron firing and dopamine release (8, 13). Thus, control of the synthesis of D2L relative to D2S is critical for proper neuronal activities (14). However, the mechanisms controlling the production of D2L relative to D2S are not yet known. Alternative pre-mRNA splicing is a powerful and versatile regulatory mechanism that produces protein diversity from a single gene, which contributes to the control of almost every cellular process (15). Tissue-or developmental stage-specific alternative RNA splicing including neuronal splicing can be explained by various combinations of ubiquitous...

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“…Most of these auxiliary cis-elements function by binding to cognate proteins (trans-factors), whereas some cis-elements function by forming a secondary structure. The majority of splicing trans-factors for ESE are serine/arginine-rich (SR) proteins, whereas the majority of splicing trans-factors for splicing silencer elements (ISSs/ESSs) are heterogeneous nuclear ribonucleic proteins (hnRNPs) [3]. Among the four classes of cis-elements, ISEs are the least characterized.…”

Section: Physiology Of Pre-mrna Splicingmentioning

confidence: 99%

Splicing Aberrations in Congenital Myasthenic Syndromes

Ohno¹

2015

JIG

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hnRNP Proteins and Splicing Control

Cited by 348 publications

References 249 publications

Repair of pre-mRNA splicing

Repair of pre-mRNA splicing

Regulatory Roles of Heterogeneous Nuclear Ribonucleoprotein M and Nova-1 Protein in Alternative Splicing of Dopamine D2 Receptor Pre-mRNA

Splicing Aberrations in Congenital Myasthenic Syndromes

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