Not only cancer: the long non-coding RNA MALAT1 affects the repertoire of alternatively spliced transcripts and circular RNAs in multiple sclerosis.


:Long non-coding RNAs (lncRNAs) are post-transcriptional and epigenetic regulators, whose implication in neurodegenerative and autoimmune diseases remains poorly understood. We analyzed publicly available microarray data sets to identify dysregulated lncRNAs in multiple sclerosis (MS), a neuroinflammatory autoimmune disease. We found a consistent upregulation in MS of the lncRNA MALAT1 (2.7-fold increase; meta-analysis, P = 1.3 × 10-8; 190 cases, 182 controls), known to regulate alternative splicing (AS). We confirmed MALAT1 upregulation in two independent MS cohorts (1.5-fold increase; P < 0.01; 59 cases, 50 controls). We hence performed MALAT1 overexpression/knockdown in cell lines, demonstrating that its modulation impacts on endogenous expression of splicing factors (HNRNPF and HNRNPH1) and on AS of MS-associated genes (IL7R and SP140). Minigene-based splicing assays upon MALAT1 modulation recapitulated IL7R and SP140 isoform unbalances observed in patients. RNA-sequencing of MALAT1-knockdown Jurkat cells further highlighted MALAT1 role in splicing (approximately 1100 significantly-modulated AS events) and revealed its contribution to backsplicing (approximately 50 differentially expressed circular RNAs). Our study proposes a possible novel role for MALAT1 dysregulation and the consequent AS alteration in MS pathogenesis, based on anomalous splicing/backsplicing profiles of MS-relevant genes.


Hum Mol Genet


Human molecular genetics


Cardamone G,Paraboschi EM,Soldà G,Cantoni C,Supino D,Piccio L,Duga S,Asselta R




Has Abstract


2019-05-01 00:00:00














  • Tagging-SNP haplotype analysis of the secretory PLA2IIa gene PLA2G2A shows strong association with serum levels of sPLA2IIa: results from the UDACS study.

    abstract::Recent prospective analysis identified secretory phospholipase A(2)-IIa (sPLA(2)IIa) as a coronary artery disease (CAD) risk predictor. This study aimed to examine the relationship between serum levels of sPLA(2)IIa and variation in the sPLA(2)IIa gene (PLA2G2A) in a cohort of patients with Type II diabetes (T2D) mell...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Wootton PT,Drenos F,Cooper JA,Thompson SR,Stephens JW,Hurt-Camejo E,Wiklund O,Humphries SE,Talmud PJ

    更新日期:2006-01-15 00:00:00

  • An L1 element intronic insertion in the black-eyed white (Mitf[mi-bw]) gene: the loss of a single Mitf isoform responsible for the pigmentary defect and inner ear deafness.

    abstract::Waardenburg syndrome type 2 (WS2) is an autosomal dominant disorder characterized by a combination of pigmentary and auditory abnormalities. Approximately 20% of WS2 cases are associated with mutations in the gene encoding microphthalmia-associated transcription factor (MITF). MITF plays a critical role in the develop...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Yajima I,Sato S,Kimura T,Yasumoto K,Shibahara S,Goding CR,Yamamoto H

    更新日期:1999-08-01 00:00:00

  • Investigating the genetic association between ERAP1 and ankylosing spondylitis.

    abstract::A strong association between ERAP1 and ankylosing spondylitis (AS) was recently identified by the Wellcome Trust Case Control Consortium and the Australo-Anglo-American Spondylitis Consortium (WTCCC-TASC) study. ERAP1 is highly polymorphic with strong linkage disequilibrium evident across the gene. We therefore conduc...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Harvey D,Pointon JJ,Evans DM,Karaderi T,Farrar C,Appleton LH,Sturrock RD,Stone MA,Oppermann U,Brown MA,Wordsworth BP

    更新日期:2009-11-01 00:00:00

  • Identification of a novel nuclear localization signal in Tbx1 that is deleted in DiGeorge syndrome patients harboring the 1223delC mutation.

    abstract::DiGeorge syndrome (DGS) is the most common human chromosomal deletion syndrome and is frequently associated with deletions on chromosome 22q11. Approximately 17% of patients with the phenotypic features of this syndrome have no detectable genomic deletion. Animal studies using mouse models have implicated Tbx1 as a cr...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Stoller JZ,Epstein JA

    更新日期:2005-04-01 00:00:00

  • Missense mutations in β-1,3-N-acetylglucosaminyltransferase 1 (B3GNT1) cause Walker-Warburg syndrome.

    abstract::Several known or putative glycosyltransferases are required for the synthesis of laminin-binding glycans on alpha-dystroglycan (αDG), including POMT1, POMT2, POMGnT1, LARGE, Fukutin, FKRP, ISPD and GTDC2. Mutations in these glycosyltransferase genes result in defective αDG glycosylation and reduced ligand binding by α...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Buysse K,Riemersma M,Powell G,van Reeuwijk J,Chitayat D,Roscioli T,Kamsteeg EJ,van den Elzen C,van Beusekom E,Blaser S,Babul-Hirji R,Halliday W,Wright GJ,Stemple DL,Lin YY,Lefeber DJ,van Bokhoven H

    更新日期:2013-05-01 00:00:00

  • Genetic regulation of gene expression in the epileptic human hippocampus.

    abstract::Epilepsy is a serious and common neurological disorder. Expression quantitative loci (eQTL) analysis is a vital aid for the identification and interpretation of disease-risk loci. Many eQTLs operate in a tissue- and condition-specific manner. We have performed the first genome-wide cis-eQTL analysis of human hippocamp...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,meta分析


    authors: Mirza N,Appleton R,Burn S,du Plessis D,Duncan R,Farah JO,Feenstra B,Hviid A,Josan V,Mohanraj R,Shukralla A,Sills GJ,Marson AG,Pirmohamed M

    更新日期:2017-05-01 00:00:00

  • Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability.

    abstract::Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA,...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Heidari A,Tongsook C,Najafipour R,Musante L,Vasli N,Garshasbi M,Hu H,Mittal K,McNaughton AJ,Sritharan K,Hudson M,Stehr H,Talebi S,Moradi M,Darvish H,Arshad Rafiq M,Mozhdehipanah H,Rashidinejad A,Samiei S,Ghadami M,

    更新日期:2015-10-15 00:00:00

  • The origin and loss of the ubiquitin activating enzyme gene on the mammalian Y chromosome.

    abstract::Mammalian sex chromosomes are thought to be descended from a homologous pair of autosomes: a testis-determining allele which defined the Y chromosome arose, recombination between the nascent X and Y chromosomes became restricted and the Y chromosome gradually lost its non-essential genetic functions. This model was or...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Mitchell MJ,Wilcox SA,Watson JM,Lerner JL,Woods DR,Scheffler J,Hearn JP,Bishop CE,Graves JA

    更新日期:1998-03-01 00:00:00

  • Homozygous mutation in the eukaryotic translation initiation factor 2alpha phosphatase gene, PPP1R15B, is associated with severe microcephaly, short stature and intellectual disability.

    abstract::Protein translation is an essential cellular process initiated by the association of a methionyl-tRNA with the translation initiation factor eIF2. The Met-tRNA/eIF2 complex then associates with the small ribosomal subunit, other translation factors and mRNA, which together comprise the translational initiation complex...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Kernohan KD,Tétreault M,Liwak-Muir U,Geraghty MT,Qin W,Venkateswaran S,Davila J,Care4Rare Canada Consortium.,Holcik M,Majewski J,Richer J,Boycott KM

    更新日期:2015-11-15 00:00:00

  • The biological impact of blood pressure-associated genetic variants in the natriuretic peptide receptor C gene on human vascular smooth muscle.

    abstract::Elevated blood pressure (BP) is a major global risk factor for cardiovascular disease. Genome-wide association studies have identified several genetic variants at the NPR3 locus associated with BP, but the functional impact of these variants remains to be determined. Here we confirmed, by a genome-wide association stu...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Ren M,Ng FL,Warren HR,Witkowska K,Baron M,Jia Z,Cabrera C,Zhang R,Mifsud B,Munroe PB,Xiao Q,Townsend-Nicholson A,Hobbs AJ,Ye S,Caulfield MJ

    更新日期:2018-01-01 00:00:00

  • Sonic Hedgehog, a key development gene, experienced intensified molecular evolution in primates.

    abstract::Sonic Hedgehog (SHH) is one of the most intensively studied genes in developmental biology. It is a highly conserved gene, found in species as diverse as arthropods and mammals. The mammalian SHH encodes a signaling molecule that plays a central role in developmental patterning, especially of the nervous system and th...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Dorus S,Anderson JR,Vallender EJ,Gilbert SL,Zhang L,Chemnick LG,Ryder OA,Li W,Lahn BT

    更新日期:2006-07-01 00:00:00

  • Identification of cis-regulatory variation influencing protein abundance levels in human plasma.

    abstract::Proteins are central to almost all cellular processes, and dysregulation of expression and function is associated with a range of disorders. A number of studies in human have recently shown that genetic factors significantly contribute gene expression variation. In contrast, very little is known about the genetic basi...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Lourdusamy A,Newhouse S,Lunnon K,Proitsi P,Powell J,Hodges A,Nelson SK,Stewart A,Williams S,Kloszewska I,Mecocci P,Soininen H,Tsolaki M,Vellas B,Lovestone S,AddNeuroMed Consortium.,Dobson R,Alzheimer's Disease Neuroimag

    更新日期:2012-08-15 00:00:00

  • CRIM1 haploinsufficiency causes defects in eye development in human and mouse.

    abstract::Colobomatous macrophthalmia with microcornea syndrome (MACOM, Online Mendelian Inheritance in Man (OMIM) 602499) is an autosomal dominantly inherited malformation of the eye, which is characterized by microcornea with increased axial length, coloboma of the iris and of the optic disc, and severe myopia. We performed w...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Beleggia F,Li Y,Fan J,Elcioğlu NH,Toker E,Wieland T,Maumenee IH,Akarsu NA,Meitinger T,Strom TM,Lang R,Wollnik B

    更新日期:2015-04-15 00:00:00

  • A feed-forward mechanism involving Drosophila fragile X mental retardation protein triggers a replication stress-induced DNA damage response.

    abstract::Fragile X syndrome, a common form of inherited mental retardation, is caused by loss of the fragile X mental retardation protein (FMRP). As a selective RNA-binding protein, FMRP is localized predominately in cytoplasm, where it regulates translational control. However, there is a small portion of FMRP present in the n...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Zhang W,Cheng Y,Li Y,Chen Z,Jin P,Chen D

    更新日期:2014-10-01 00:00:00

  • Enhanced excitation-coupled Ca(2+) entry induces nuclear translocation of NFAT and contributes to IL-6 release from myotubes from patients with central core disease.

    abstract::Prolonged depolarization of skeletal muscle cells induces entry of extracellular calcium into muscle cells, an event referred to as excitation-coupled calcium entry. Skeletal muscle excitation-coupled calcium entry relies on the interaction between the 1,4-dihydropyridine receptor on the sarcolemma and the ryanodine r...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Treves S,Vukcevic M,Jeannet PY,Levano S,Girard T,Urwyler A,Fischer D,Voit T,Jungbluth H,Lillis S,Muntoni F,Quinlivan R,Sarkozy A,Bushby K,Zorzato F

    更新日期:2011-02-01 00:00:00

  • Over-expression of BCL2 rescues muscle weakness in a mouse model of oculopharyngeal muscular dystrophy.

    abstract::Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscular dystrophy caused by a polyalanine expansion mutation in the coding region of the poly-(A) binding protein nuclear 1 (PABPN1) gene. In unaffected individuals, (GCG)(6) encodes the first 6 alanines in a homopolymeric stretch of 10 alanines. In most patie...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Davies JE,Rubinsztein DC

    更新日期:2011-03-15 00:00:00

  • Mitochondrial DNA polymerase-gamma and human disease.

    abstract::The maintenance of mitochondrial DNA (mtDNA) is critically dependent upon polymerase-gamma (pol-gamma), encoded by the nuclear gene POLG. Over the last 5 years, it has become clear that mutations of POLG are a major cause of human disease. Secondary mtDNA defects characterize these disorders, with mtDNA depletion, mul...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,评审


    authors: Hudson G,Chinnery PF

    更新日期:2006-10-15 00:00:00

  • Looking beyond the genes: the role of non-coding variants in human disease.

    abstract::Over the past decades the search for disease causing variants has been focusing exclusively on the coding genome. This highly selective approach has been extremely successful resulting in the identification of thousands of disease genes, but ignores the functional and therefore disease relevance of the rest of the gen...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Spielmann M,Mundlos S

    更新日期:2016-10-01 00:00:00

  • Defects in myelination, paranode organization and Purkinje cell innervation in the ether lipid-deficient mouse cerebellum.

    abstract::Ether lipids (ELs), particularly plasmalogens, are essential constituents of the mammalian central nervous system. The physiological role of ELs, in vivo, however is still enigmatic. In the present study, we characterized a mouse model carrying a targeted deletion of the peroxisomal dihydroxyacetonephosphate acyltrans...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Teigler A,Komljenovic D,Draguhn A,Gorgas K,Just WW

    更新日期:2009-06-01 00:00:00

  • Methylation imprints of the imprint control region of the SNRPN-gene in human gametes and preimplantation embryos.

    abstract::Imprinting is an epigenetic mechanism leading to mono-allelic expression of imprinted genes. In order to inherit the differential epigenetic imprints from one generation to the next, these imprints have to be erased in the primordial germ cells and re-established in a sex-specific manner during gametogenesis. The exac...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Geuns E,De Rycke M,Van Steirteghem A,Liebaers I

    更新日期:2003-11-15 00:00:00

  • Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle.

    abstract::Plasmid pRSVL persisted and expressed luciferase for at least 19 months in mouse skeletal muscle after intramuscular injection. Other injected plasmids also stably expressed long-term suggesting that any plasmid DNA could stably persist and express in muscle. Plasmid DNA was demonstrated by quantitative PCR in some of...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Wolff JA,Ludtke JJ,Acsadi G,Williams P,Jani A

    更新日期:1992-09-01 00:00:00

  • Junctional epidermolysis bullosa inversa (locus EBR2A) assigned to 1q31 by linkage and association to LAMC1.

    abstract::Junctional epidermolysis bullosa inversa is an autosomal recessive blistering skin disease with an ultrastructural hemidesmosome defect similar to that of the Herlitz disease, yet with a non-lethal and different course of the disease. Its delineation is based on five geographically associated Norwegian families where ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Gedde-Dahl T Jr,Dupuy BM,Jonassen R,Winberg JO,Anton-Lamprecht I,Olaisen B

    更新日期:1994-08-01 00:00:00

  • Familial paroxysmal kinesigenic dyskinesia is associated with mutations in the KCNA1 gene.

    abstract::Paroxysmal kinesigenic dyskinesia (PKD) is a heterogeneous movement disorder characterized by recurrent dyskinesia attacks triggered by sudden movement. PRRT2 has been identified as the first causative gene of PKD. However, it is only responsible for approximately half of affected individuals, indicating that other lo...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Yin XM,Lin JH,Cao L,Zhang TM,Zeng S,Zhang KL,Tian WT,Hu ZM,Li N,Wang JL,Guo JF,Wang RX,Xia K,Zhang ZH,Yin F,Peng J,Liao WP,Yi YH,Liu JY,Yang ZX,Chen Z,Mao X,Yan XX,Jiang H,Shen L,Chen SD,Zhang LM,Tan

    更新日期:2018-02-15 00:00:00

  • Depletion of p62 reduces nuclear inclusions and paradoxically ameliorates disease phenotypes in Huntington's model mice.

    abstract::Huntington's disease (HD) is a dominantly inherited genetic disease caused by mutant huntingtin (htt) protein with expanded polyglutamine (polyQ) tracts. A neuropathological hallmark of HD is the presence of neuronal inclusions of mutant htt. p62 is an important regulatory protein in selective autophagy, a process by ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Kurosawa M,Matsumoto G,Kino Y,Okuno M,Kurosawa-Yamada M,Washizu C,Taniguchi H,Nakaso K,Yanagawa T,Warabi E,Shimogori T,Sakurai T,Hattori N,Nukina N

    更新日期:2015-02-15 00:00:00

  • Ataxin-1 regulates the cerebellar bioenergetics proteome through the GSK3β-mTOR pathway which is altered in Spinocerebellar ataxia type 1 (SCA1).

    abstract::A polyglutamine expansion within the ataxin-1 protein (ATXN1) underlies spinocerebellar ataxia type-1 (SCA1), a neurological disorder mainly characterized by ataxia and cerebellar deficits. In SCA1, both loss and gain of ATXN1 biological functions contribute to cerebellar pathogenesis. However, the critical ATXN1 func...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Sánchez I,Balagué E,Matilla-Dueñas A

    更新日期:2016-09-15 00:00:00

  • Characterization of myotonic dystrophy kinase (DMK) protein in human and rodent muscle and central nervous tissue.

    abstract::Myotonic dystrophy (DM) is the most common form of inherited neuromuscular disease in adults and is characterized by progressive muscle wasting and myotonia. The mutation responsible for DM has been identified as the amplification of a polymorphic (CTG)n repeat in the 3' untranslated region of a gene encoding a serine...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Whiting EJ,Waring JD,Tamai K,Somerville MJ,Hincke M,Staines WA,Ikeda JE,Korneluk RG

    更新日期:1995-06-01 00:00:00

  • Characterization of molecular defects in xeroderma pigmentosum group F in relation to its clinically mild symptoms.

    abstract::Xeroderma pigmentosum (XP) complementation group F was first reported in Japan and most XP-F patients reported to date are Japanese. The clinical features of XP-F patients are rather mild, including late onset of skin cancer. Recently a cDNA that corrects the repair deficiency of cultured XP-F cells was isolated. The ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Matsumura Y,Nishigori C,Yagi T,Imamura S,Takebe H

    更新日期:1998-06-01 00:00:00

  • Association of prolactin receptor (PRLR) variants with prolactinomas.

    abstract::Prolactinomas are the most frequent type of pituitary tumors, which represent 10-20% of all intracranial neoplasms in humans. Prolactinomas develop in mice lacking the prolactin receptor (PRLR), which is a member of the cytokine receptor superfamily that signals via Janus kinase-2-signal transducer and activator of tr...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Gorvin CM,Newey PJ,Rogers A,Stokes V,Neville MJ,Lines KE,Ntali G,Lees P,Morrison PJ,Singhellakis PN,Malandrinou FC,Karavitaki N,Grossman AB,Karpe F,Thakker RV

    更新日期:2019-03-15 00:00:00

  • Mutations in XRCC4 cause primary microcephaly, short stature and increased genomic instability.

    abstract::DNA double-strand breaks (DSBs) are highly toxic lesions, which, if not properly repaired, can give rise to genomic instability. Non-homologous end-joining (NHEJ), a well-orchestrated, multistep process involving numerous proteins essential for cell viability, represents one major pathway to repair DSBs in mammalian c...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Rosin N,Elcioglu NH,Beleggia F,Isgüven P,Altmüller J,Thiele H,Steindl K,Joset P,Rauch A,Nürnberg P,Wollnik B,Yigit G

    更新日期:2015-07-01 00:00:00

  • Reduced AKT/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model.

    abstract::Rett syndrome (RTT) is a neurodevelopmental disorder with no efficient treatment that is caused in the majority of cases by mutations in the gene methyl-CpG binding-protein 2 (MECP2). RTT becomes manifest after a period of apparently normal development and causes growth deceleration, severe psychomotor impairment and ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章


    authors: Ricciardi S,Boggio EM,Grosso S,Lonetti G,Forlani G,Stefanelli G,Calcagno E,Morello N,Landsberger N,Biffo S,Pizzorusso T,Giustetto M,Broccoli V

    更新日期:2011-03-15 00:00:00