Protection of p27Kip1 mRNA by quaking RNA binding proteins promotes oligodendrocyte differentiation

Larocque, Daniel; Galarneau, André; Liu, Hsueh‐Ning; Scott, Michelle S.; Almazán, Guillermina; Richard, Stéphane

doi:10.1038/nn1359

Cited by 154 publications

(206 citation statements)

References 48 publications

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“…QKI is a mammalian RNAbinding protein that regulates translational control (50), alternative splicing (51), RNA export (52), and RNA stability (53,54). The identification of the same binding site for BBP and QKI is not surprising since there is 70% sequence identity (14 of 20 amino acids) and 85% sequence similarity (17 of 20 amino acids) in the residues contacting the core UACUAAC sequence.…”

Section: Specificity Of Bbp Compared With Other Kh Domain Proteins-mentioning

confidence: 99%

An Extended RNA Binding Site for the Yeast Branch Point-binding Protein and the Role of Its Zinc Knuckle Domains in RNA Binding

Garrey¹,

Voelker²,

Berglund

2006

Journal of Biological Chemistry

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The highly conserved branch point sequence (BPS) of UAC-UAAC in Saccharomyces cerevisiae is initially recognized by the branch point-binding protein (BBP). Using systematic evolution of ligands by exponential enrichment we have determined that yeast BBP binds the branch point sequence UACUAAC with highest affinity and prefers an additional adenosine downstream of the BPS. Furthermore, we also found that a stem-loop upstream of the BPS enhances binding both to an artificially designed RNA (30-fold effect) and to an RNA from a yeast intron (3-fold effect). The zinc knuckles of BBP are partially responsible for the enhanced binding to the stem-loop but do not appear to have a significant role in the binding of BBP to single-strand RNA substrates. C-terminal deletions of BBP reveal that the linker regions between the two zinc knuckles and between the N-terminal RNA binding domains (KH and QUA2 domains) and the first zinc knuckle are important for binding to RNA. The lack of involvement of the second highly conserved zinc knuckle in RNA binding suggests that this zinc knuckle plays a different role in RNA processing than enhancing the binding of BBP to the BPS.The branch point-binding protein (BBP) 4 in Saccharomyces cerevisiae is an RNA-binding protein that is thought to be the first protein to bind the branch point sequence (BPS) during splicing. In yeast BBP binds to the highly invariant branch point sequence UACUAAC (branch point A is underlined), recognizing every nucleotide (1). BBP binds the BPS in the second commitment complex (CC2) and is necessary for stable formation of this complex (2). Splicing factor 1 (SF1), the human orthologue of BBP, is a more promiscuous RNA-binding protein, recognizing a degenerate sequence, CURAY (R ϭ purine, Y ϭ pyrimidine), in which only the U and A are critical (1). When discussing the yeast branch point-binding protein we will use the term BBP, when discussing the human protein we will use the term SF1, and when discussing both proteins we will use the term BBP/SF1. In the mammalian system, the equivalent complex to the yeast CC2 is the E complex in which SF1 binds the BPS (3, 4). In addition to recognizing the BPS, BBP/SF1 plays an important role in bridging the 5Ј end and 3Ј end of the intron by interacting with U1 snRNP at the 5Ј splice site and Mud2p at the 3Ј end of yeast introns and U2AF65 at the 3Ј end of human introns (5-8). BBP/SF1 is replaced at the BPS by U2 snRNP in an ATP-dependent step that leads to the formation of A complex (9, 10).BBP/SF1 contains multiple domains, many of which are conserved between yeast and human (Fig. 1). The BBP/SF1 N-terminal domain interacts with Mud2p in yeast and U2AF65 in humans (5,6,8). The C terminus contains a proline-rich domain, which in yeast interacts with Prp40, a component of the U1 snRNP (7). FBP11, a potential vertebrate homologue of Prp40, binds to the proline-rich domain of human SF1 (11).One of the most highly conserved regions of BBP/SF1 encompasses the RNA binding domains (Fig. 1). The region of BBP/SF1 responsible...

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Section: Specificity Of Bbp Compared With Other Kh Domain Proteins-mentioning

confidence: 99%

An Extended RNA Binding Site for the Yeast Branch Point-binding Protein and the Role of Its Zinc Knuckle Domains in RNA Binding

Garrey¹,

Voelker²,

Berglund

2006

Journal of Biological Chemistry

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“…Because other types of QRE elements have also been described (9-12), we therefore attempted to find other QREs for the remaining three genes (CDKN1B, MAG, and TF). An experimentally verified QRE that contains the bipartite consensus sequence has been identified in the coding sequence of Cdkn1b in mouse (10). In human CDKN1B, the sequence of the mouse QRE is fairly well conserved ( Fig.…”

mentioning

confidence: 99%

“…The Qki gene contains an RNA-binding domain (KH domain) that binds directly to cellular RNA (8). Several different sequence motifs have been identified as targets for the Qki protein (9)(10)(11)(12). One of these Qki response elements (QREs) consists of a bipartite consensus sequence that has been shown to bind the Qki protein in vivo in at least 23 different mouse mRNA species (9).…”

mentioning

confidence: 99%

“…This mouse protein directly regulates the expression of at least one myelin-specific gene, e.g., myelin basic protein (Mbp) (1), and controls the alternative splicing of the myelin-associated glycoprotein (Mag) (12). In addition, Qki protein regulates the cell cycle inhibitor cyclin-dependent kinase inhibitor 1B (Cdkn1b) (10), which is involved in the terminal differentiation of oligodendrocytes (13). Cdkn1b also activates the mouse Mbp promoter through interaction with the transcription factor sexdetermining region Y-box10 (Sox10) (14,15).…”

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confidence: 99%

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Human QKI, a potential regulator of mRNA expression of human oligodendrocyte-related genes involved in schizophrenia

Åberg

Saetre

Jareborg

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

193

159

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The quaking viable mouse mutation (qk v ) is a deletion including the 5 regulatory region of the quaking gene (Qki), which causes body tremor and severe dysmyelination in mouse. The function of the human quaking gene, called quaking homolog KH domain RNAbinding (mouse) (QKI), is not well known. We have previously shown that QKI is a new candidate gene for schizophrenia. Here we show that human QKI mRNA levels can account for a high proportion (47%) of normal interindividual mRNA expression variation (and covariation) of six oligodendrocyte-related genes (PLP1, MAG, MBP, TF, SOX10, and CDKN1B) in 55 human brain autopsy samples from individuals without psychiatric diagnoses. In addition, the tightly coexpressed myelin-related genes (PLP1, MAG, and TF) have decreased mRNA levels in 55 schizophrenic patients, as compared with 55 control individuals, and most of this difference (68 -96%) can be explained by variation in the relative mRNA levels of QKI-7kb, the same QKI splice variant previously shown to be down-regulated in patients with schizophrenia. Taken together, our results suggest that QKI levels may regulate oligodendrocyte differentiation and maturation in human brain, in a similar way as in mouse. Moreover, we hypothesize that previously observed decreased activity of myelin-related genes in schizophrenia might be caused by disturbed QKI splicing.myelin ͉ quaking ͉ splice variant

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“…The importance of cell-cycle inhibitors in oligodendrocyte differentiation was further suggested by reports of alternative biological functions for these molecules. P27Kip, for instance, was identified as part of a transcriptional complex activating the MBP promoter (Miskimins et al 2002), as well as part of a complex with specific RNA-binding proteins like Qki (Larocque et al 2005). Despite these exciting findings, overexpression of cell-cycle inhibitors per se was not sufficient to induce differentiation (Tikoo et al 1998;Tang et al 1999) and suggested that additional events must be responsible for the differentiation of progenitors into mature oligodendrocytes.…”

Section: Model 3 Differentiation Consequent To Hdac-mediated Repressimentioning

confidence: 99%

Post-Translational Modifications of Nucleosomal Histones in Oligodendrocyte Lineage Cells in Development and Disease

Shen

Casaccia‐Bonnefil

2007

J Mol Neurosci

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The role of epigenetics in modulating gene expression in the development of organs and tissues and in disease states is becoming increasingly evident. Epigenetics refers to the several mechanisms modulating inheritable changes in gene expression that are independent of modifications of the primary DNA sequence and include post-translational modifications of nucleosomal histones, changes in DNA methylation, and the role of microRNA. This review focuses on the epigenetic regulation of gene expression in oligodendroglial lineage cells. The biological effects that posttranslational modifications of critical residues in the N-terminal tails of nucleosomal histones have on oligodendroglial cells are reviewed, and the implications for disease and repair are critically discussed.

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Protection of p27Kip1 mRNA by quaking RNA binding proteins promotes oligodendrocyte differentiation

Cited by 154 publications

References 48 publications

An Extended RNA Binding Site for the Yeast Branch Point-binding Protein and the Role of Its Zinc Knuckle Domains in RNA Binding

An Extended RNA Binding Site for the Yeast Branch Point-binding Protein and the Role of Its Zinc Knuckle Domains in RNA Binding

Human QKI, a potential regulator of mRNA expression of human oligodendrocyte-related genes involved in schizophrenia

Post-Translational Modifications of Nucleosomal Histones in Oligodendrocyte Lineage Cells in Development and Disease

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