Functional splicing network reveals extensive regulatory potential of the core spliceosomal machinery.


:Pre-mRNA splicing relies on the poorly understood dynamic interplay between >150 protein components of the spliceosome. The steps at which splicing can be regulated remain largely unknown. We systematically analyzed the effect of knocking down the components of the splicing machinery on alternative splicing events relevant for cell proliferation and apoptosis and used this information to reconstruct a network of functional interactions. The network accurately captures known physical and functional associations and identifies new ones, revealing remarkable regulatory potential of core spliceosomal components, related to the order and duration of their recruitment during spliceosome assembly. In contrast with standard models of regulation at early steps of splice site recognition, factors involved in catalytic activation of the spliceosome display regulatory properties. The network also sheds light on the antagonism between hnRNP C and U2AF, and on targets of antitumor drugs, and can be widely used to identify mechanisms of splicing regulation.


Mol Cell


Molecular cell


Papasaikas P,Tejedor JR,Vigevani L,Valcárcel J




Has Abstract


2015-01-08 00:00:00














  • hnRNP A1 proofreads 3' splice site recognition by U2AF.

    abstract::One of the earliest steps in metazoan pre-mRNA splicing involves binding of U2 snRNP auxiliary factor (U2AF) 65 KDa subunit to the polypyrimidine (Py) tract and of the 35 KDa subunit to the invariant AG dinucleotide at the intron 3' end. Here we use in vitro and in vivo depletion, as well as reconstitution assays usin...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Tavanez JP,Madl T,Kooshapur H,Sattler M,Valcárcel J

    更新日期:2012-02-10 00:00:00

  • Nhp6, an HMG1 protein, functions in SNR6 transcription by RNA polymerase III in S. cerevisiae.

    abstract::Nhp6A and Nhp6B are HMG1-like proteins required for the growth of S. cerevisiae at elevated temperatures. We show that the conditional lethality of an nhp6 strain results from defective transcription of SNR6 (U6 snRNA) by RNA polymerase III. Overexpression of U6 snRNA or Brf1, a limiting component of TFIIIB, and an ac...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Kruppa M,Moir RD,Kolodrubetz D,Willis IM

    更新日期:2001-02-01 00:00:00

  • How Rho exerts its muscle on RNA.

    abstract::Rho factor in bacteria terminates transcription by using energy from ATP hydrolysis to forcefully dissociate the transcripts from RNA polymerase. used data from presteady-state ATPase kinetics to support a rational mechanistic model for Rho's action on RNA. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章,评审


    authors: Richardson JP

    更新日期:2006-06-23 00:00:00

  • Linking differential chromatin loops to transcriptional decisions.

    abstract::GATA-1 and GATA-2 control proliferation and differentiation of hematopoietic progenitor cells via transcriptional regulation. In this issue of Molecular Cell, Jing et al. (2008) demonstrate that GATA factor exchange on the Kit locus directs a transcriptional switch by reconfiguring chromatin loops. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Apostolou E,Thanos D

    更新日期:2008-02-01 00:00:00

  • METTL3 Gains R/W Access to the Epitranscriptome.

    abstract::Epitranscriptomic marks are dynamically placed on mRNA by "writer" or "eraser" enzymes, while "readers" modulate their function accordingly. Lin et al. (2016) now report that the N6-methyladenosine:RNA methyltransferase METTL3 is both a writer and a reader, directly enhancing mRNA translation. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Schumann U,Shafik A,Preiss T

    更新日期:2016-05-05 00:00:00

  • A Reply to "MNase-Sensitive Complexes in Yeast: Nucleosomes and Non-histone Barriers," by Chereji et al.

    abstract::In this issue of Molecular Cell, Chereji et al. (2017) present new data on MNase-sensitive particles previously identified upstream of transcription start sites at many promoters in budding yeast, and they argue, based upon negative histone-ChIP results, that they are non-nucleosomal signals generated by transcription...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Kubik S,Bruzzone MJ,Albert B,Shore D

    更新日期:2017-02-02 00:00:00

  • KAP1 Recruitment of the 7SK snRNP Complex to Promoters Enables Transcription Elongation by RNA Polymerase II.

    abstract::The transition from transcription initiation to elongation at promoters of primary response genes (PRGs) in metazoan cells is controlled by inducible transcription factors, which utilize P-TEFb to phosphorylate RNA polymerase II (Pol II) in response to stimuli. Prior to stimulation, a fraction of P-TEFb is recruited t...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: McNamara RP,Reeder JE,McMillan EA,Bacon CW,McCann JL,D'Orso I

    更新日期:2016-01-07 00:00:00

  • Construction of the Central Protuberance and L1 Stalk during 60S Subunit Biogenesis.

    abstract::Ribosome assembly is driven by numerous assembly factors, including the Rix1 complex and the AAA ATPase Rea1. These two assembly factors catalyze 60S maturation at two distinct states, triggering poorly understood large-scale structural transitions that we analyzed by cryo-electron microscopy. Two nuclear pre-60S inte...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Kater L,Mitterer V,Thoms M,Cheng J,Berninghausen O,Beckmann R,Hurt E

    更新日期:2020-08-20 00:00:00

  • Hos1 deacetylates Smc3 to close the cohesin acetylation cycle.

    abstract::Cohesion between sister chromatids is mediated by the chromosomal cohesin complex. In budding yeast, cohesin is loaded onto chromosomes during the G1 phase of the cell cycle. During S phase, the replication fork-associated acetyltransferase Eco1 acetylates the cohesin subunit Smc3 to promote the establishment of siste...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Borges V,Lehane C,Lopez-Serra L,Flynn H,Skehel M,Rolef Ben-Shahar T,Uhlmann F

    更新日期:2010-09-10 00:00:00

  • Atg8 transfer from Atg7 to Atg3: a distinctive E1-E2 architecture and mechanism in the autophagy pathway.

    abstract::Atg7 is a noncanonical, homodimeric E1 enzyme that interacts with the noncanonical E2 enzyme, Atg3, to mediate conjugation of the ubiquitin-like protein (UBL) Atg8 during autophagy. Here we report that the unique N-terminal domain of Atg7 (Atg7(NTD)) recruits a unique "flexible region" from Atg3 (Atg3(FR)). The struct...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Taherbhoy AM,Tait SW,Kaiser SE,Williams AH,Deng A,Nourse A,Hammel M,Kurinov I,Rock CO,Green DR,Schulman BA

    更新日期:2011-11-04 00:00:00

  • An Arginine Nexus in the RNA Polymerase II CTD.

    abstract::In this issue of Molecular Cell,Sharma et al. (2019) show that normal cell growth requires conversion of an arginine residue in the RNA polymerase II C-terminal domain (CTD) to citrulline, uncovering a potential regulatory pathway involving opposing arginine modifications. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Corden JL

    更新日期:2019-01-03 00:00:00

  • The Mitochondrial Basis of Aging.

    abstract::A decline in mitochondrial quality and activity has been associated with normal aging and correlated with the development of a wide range of age-related diseases. Here, we review the evidence that a decline in mitochondria function contributes to aging. In particular, we discuss how mitochondria contribute to specific...

    journal_title:Molecular cell

    pub_type: 杂志文章,评审


    authors: Sun N,Youle RJ,Finkel T

    更新日期:2016-03-03 00:00:00

  • The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility.

    abstract::During meiosis, the homologous chromosomes pair and recombine. An evolutionarily conserved protein structure, the synaptonemal complex (SC), is located along the paired meiotic chromosomes. We have studied the function of a structural component in the axial/lateral element of the SC, the synaptonemal complex protein 3...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Yuan L,Liu JG,Zhao J,Brundell E,Daneholt B,Höög C

    更新日期:2000-01-01 00:00:00

  • β-Hydroxybutyrate Prevents Vascular Senescence through hnRNP A1-Mediated Upregulation of Oct4.

    abstract::β-hydroxybutyrate (β-HB) elevation during fasting or caloric restriction is believed to induce anti-aging effects and alleviate aging-related neurodegeneration. However, whether β-HB alters the senescence pathway in vascular cells remains unknown. Here we report that β-HB promotes vascular cell quiescence, which signi...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Han YM,Bedarida T,Ding Y,Somba BK,Lu Q,Wang Q,Song P,Zou MH

    更新日期:2018-09-20 00:00:00

  • A dynamic role of HAUSP in the p53-Mdm2 pathway.

    abstract::Our previous study showed that ubiquitination of p53 is reversible and that the ubiquitin hydrolase HAUSP can stabilize p53 by deubiquitination. Here, we found that partial reduction of endogenous HAUSP levels by RNAi indeed destabilizes endogenous p53; surprisingly, however, nearly complete ablation of HAUSP stabiliz...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Li M,Brooks CL,Kon N,Gu W

    更新日期:2004-03-26 00:00:00

  • Smad about E2F. TGFbeta repressionof c-Myc via a Smad3/E2F/p107 complex.

    abstract::Signaling by TGFbeta regulates the expression of hundreds of genes. The rapid repression of c-Myc stands out because of its roles in growth control and cancer. Recent work shows that c-Myc repression by TGFbeta is mediated by the nuclear translocation of a novel, preformed complex composed of Smad3, E2F4 or E2F5, and ...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Kowalik TF

    更新日期:2002-07-01 00:00:00

  • Spoon-Feeding Ribosomes to Autophagy.

    abstract::The ribosome, a ribonucleoprotein machine for protein synthesis, can also serve as an abundant nutrient source under starvation conditions. In a recent issue of Science, Wyant et al. (2018) discovered a specialized "spoon" to "scoop up" more ribosomes for degradation by autophagy. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Nakatogawa H

    更新日期:2018-07-19 00:00:00

  • FANCM and FAAP24 function in ATR-mediated checkpoint signaling independently of the Fanconi anemia core complex.

    abstract::The Fanconi anemia (FA) pathway is implicated in DNA repair and cancer predisposition. Central to this pathway is the FA core complex, which is targeted to chromatin by FANCM and FAAP24 following replication stress. Here we show that FANCM and FAAP24 interact with the checkpoint protein HCLK2 independently of the FA c...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Collis SJ,Ciccia A,Deans AJ,Horejsí Z,Martin JS,Maslen SL,Skehel JM,Elledge SJ,West SC,Boulton SJ

    更新日期:2008-11-07 00:00:00

  • ATM breaks into heterochromatin.

    abstract::Heterochromatin is refractory to DNA transactions, including repair. In a recent issue of Molecular Cell, Goodarzi et al. (2008) reveal how the central transducing kinase of the DNA damage response relieves this natural barrier by increasing heterochromatic DNA accessibility. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Fernandez-Capetillo O,Nussenzweig A

    更新日期:2008-08-08 00:00:00

  • Context-specific regulation of NF-κB target gene expression by EZH2 in breast cancers.

    abstract::Both EZH2 and NF-κB contribute to aggressive breast cancer, yet whether the two oncogenic factors have functional crosstalk in breast cancer is unknown. Here, we uncover an unexpected role of EZH2 in conferring the constitutive activation of NF-κB target gene expression in ER-negative basal-like breast cancer cells. T...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Lee ST,Li Z,Wu Z,Aau M,Guan P,Karuturi RK,Liou YC,Yu Q

    更新日期:2011-09-02 00:00:00

  • Structural Basis of Transcription Inhibition by Fidaxomicin (Lipiarmycin A3).

    abstract::Fidaxomicin is an antibacterial drug in clinical use for treatment of Clostridium difficile diarrhea. The active ingredient of fidaxomicin, lipiarmycin A3 (Lpm), functions by inhibiting bacterial RNA polymerase (RNAP). Here we report a cryo-EM structure of Mycobacterium tuberculosis RNAP holoenzyme in complex with Lpm...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Lin W,Das K,Degen D,Mazumder A,Duchi D,Wang D,Ebright YW,Ebright RY,Sineva E,Gigliotti M,Srivastava A,Mandal S,Jiang Y,Liu Y,Yin R,Zhang Z,Eng ET,Thomas D,Donadio S,Zhang H,Zhang C,Kapanidis AN,Ebright RH

    更新日期:2018-04-05 00:00:00

  • Structures of Neisseria meningitidis Cas9 Complexes in Catalytically Poised and Anti-CRISPR-Inhibited States.

    abstract::High-resolution Cas9 structures have yet to reveal catalytic conformations due to HNH nuclease domain positioning away from the cleavage site. Nme1Cas9 and Nme2Cas9 are compact nucleases for in vivo genome editing. Here, we report structures of meningococcal Cas9 homologs in complex with sgRNA, dsDNA, or the AcrIIC3 a...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Sun W,Yang J,Cheng Z,Amrani N,Liu C,Wang K,Ibraheim R,Edraki A,Huang X,Wang M,Wang J,Liu L,Sheng G,Yang Y,Lou J,Sontheimer EJ,Wang Y

    更新日期:2019-12-19 00:00:00

  • Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs.

    abstract::Argonaute proteins associate with small RNAs that guide mRNA degradation, translational repression, or a combination of both. The human Argonaute family has eight members, four of which (Ago1 through Ago4) are closely related and coexpressed in many cell types. To understand the biological function of the different Ag...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Meister G,Landthaler M,Patkaniowska A,Dorsett Y,Teng G,Tuschl T

    更新日期:2004-07-23 00:00:00

  • Inflating cell numbers by Wnt.

    abstract::One of the prominent biological phenomena controlled by Wnt signaling is the expansion of cells with predefined fates. In the November 27, 2002, issue of Cell, Rosenfeld and colleagues describe an example of Wnt-controlled proliferation during genesis of the cardiac outflow tract and the pituitary gland. As a downstre...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Clevers H

    更新日期:2002-12-01 00:00:00

  • Methyl-Metabolite Depletion Elicits Adaptive Responses to Support Heterochromatin Stability and Epigenetic Persistence.

    abstract::S-adenosylmethionine (SAM) is the methyl-donor substrate for DNA and histone methyltransferases that regulate epigenetic states and subsequent gene expression. This metabolism-epigenome link sensitizes chromatin methylation to altered SAM abundance, yet the mechanisms that allow organisms to adapt and protect epigenet...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Haws SA,Yu D,Ye C,Wille CK,Nguyen LC,Krautkramer KA,Tomasiewicz JL,Yang SE,Miller BR,Liu WH,Igarashi K,Sridharan R,Tu BP,Cryns VL,Lamming DW,Denu JM

    更新日期:2020-04-16 00:00:00

  • BRCA1 recruitment to transcriptional pause sites is required for R-loop-driven DNA damage repair.

    abstract::The mechanisms contributing to transcription-associated genomic instability are both complex and incompletely understood. Although R-loops are normal transcriptional intermediates, they are also associated with genomic instability. Here, we show that BRCA1 is recruited to R-loops that form normally over a subset of tr...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Hatchi E,Skourti-Stathaki K,Ventz S,Pinello L,Yen A,Kamieniarz-Gdula K,Dimitrov S,Pathania S,McKinney KM,Eaton ML,Kellis M,Hill SJ,Parmigiani G,Proudfoot NJ,Livingston DM

    更新日期:2015-02-19 00:00:00

  • Just the FACTs: histone H2B ubiquitylation and nucleosome dynamics.

    abstract::In this issue of Molecular Cell, Fleming et al. (2008) show that histone H2B ubiquitylation and FACT function interdependently to facilitate nucleosome reassembly during transcription elongation, thereby demonstrating that histone posttranslational modifications can provide important but transient transcriptional sign...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Hartzog GA,Quan TK

    更新日期:2008-07-11 00:00:00

  • MacroH2A1 and ATM Play Opposing Roles in Paracrine Senescence and the Senescence-Associated Secretory Phenotype.

    abstract::Oncogene-induced senescence (OIS) is a tumor-suppressive mechanism typified by stable proliferative arrest, a persistent DNA damage response, and the senescence-associated secretory phenotype (SASP), which helps to maintain the senescent state and triggers bystander senescence in a paracrine fashion. Here, we demonstr...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Chen H,Ruiz PD,McKimpson WM,Novikov L,Kitsis RN,Gamble MJ

    更新日期:2015-09-03 00:00:00

  • Histone acetylation by HBO1 tightens replication licensing.

    abstract::In this issue of Molecular Cell, Miotto and Struhl (2010) suggest that replication licensing, the loading of Mcm2-7 onto DNA, is promoted by HBO1 acetylating histone H4 at replication origins, providing a molecular view of how chromatin status influences origin usage. ...

    journal_title:Molecular cell

    pub_type: 评论,杂志文章


    authors: Chadha GS,Blow JJ

    更新日期:2010-01-15 00:00:00

  • Distinct signals generate repeating striped pattern in the embryonic parasegment.

    abstract::How repeating striped patterns arise across cellular fields is unclear. To address this we examined the repeating pattern of Stripe (Sr) expression across the parasegment (PS) in Drosophila. This pattern is generated in two steps. First, the ligands Hedgehog (Hh) and Wingless (Wg) subdivide the PS into smaller territo...

    journal_title:Molecular cell

    pub_type: 杂志文章


    authors: Hatini V,DiNardo S

    更新日期:2001-01-01 00:00:00