Communication of the Position of Exon-Exon Junctions to the mRNA Surveillance Machinery by the Protein RNPS1

Lykke-Andersen, Jens; Shu, Mei‐Di; Steitz, Joan A.

doi:10.1126/science.1062786

Cited by 360 publications

(352 citation statements)

References 29 publications

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“…It was also shown that RNPS1 remains on the mature mRNA at the position of an exon-exon junction (Le Hir et al, 2000). This complex seems to be important for the transport of the mRNA to the cytoplasm and also seems to have a function in differentiating premature and correct stop codons (Lykke-Andersen et al, 2001). …”

Section: Some Of the Most Important Ones Arementioning

confidence: 99%

Promoter-driven splicing regulation in fission yeast

Moldón

Malapeira

Gabrielli

et al. 2008

Nature

135

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AGRADECIMIENTOS vi viiDurante toda esta tesis veía clarísimo todo lo que escribir en este apartado y ahora que llega el momento me quedo en blanco... Debe ser la presión de saber que va a ser la sección más leída… Primero agradecer a José y a Elena el poder haber trabajado en este laboratorio durante este tiempo. Han sido casi dos tesis, sí, sí, mi primera página del cuaderno de laboratorio data del 19 de Abril del 2000, todavía recuerdo el primer día, lo primero que hice fue rotular eppendorfs con una temblorosa mano, cuántos nervios. Después de trabajar en muchos temas, momentos difíciles y agradables, odiosos y entrañables, mudanzas, meetings, reuniones, cenas y mil otros recuerdos que me llevo puedo decir que me va a costar estar lejos de este lugar. Un abrazo muy fuerte a los dos!! Mis compañeros de laboratorio, pasados, presentes y futuros, desde aquel chico de la UAB que me enseñó como utilizar una enzima de restricción hasta el chico nuevo que todavía no conozco... No tengo palabras. Habéis sido mi familia todo este tiempo:A la pequeña Ester que me ha cuidado desde el principio como una hermana mayor. A Ana con la que el odio y el cariño se entrelazaban continuamente, muy buena conversadora y con gran ojo crítico. A Carine cuya breve estancia me dejó entrever que hay más de una manera de hacer ciencia. A Jordi (MalaP), compañero de adversidades y aventuras. A Mercè, cuyo apoyo logístico y moral ha sido imprescindible. A Alice, símbolo de la ternura y de la filología italiana, ya se sabe, a caballo donato... A Miriam, una de las mejores personas que conozco, sensata, seria y muy inteligente, una gran científica. A Mónica, maestra de artes marciales y colis. A Blanca, la dulzura personificada y buen público para los chistes. A Nati, también compañera de poyata, penas y alegrías, una post-doc todavía sin título. A Isabel, la catol... una gran amiga y compañera de ChIPs, tranquila que las cosas se van arreglando solas! A Sarela, un meiga pero de las buenas y a Iván (el granaíno), que con su corta pero intensa estancia nos alegró las largas horas de laboratorio. A todos gracias por apoyarme, aguantarme y porque nadie mejor que vosotros sabe lo que supone esta tesis.Al resto de gente de la UPF, los vecinos de laboratorio, especialmente el laboratorio de Señalización Celular (o cariñosamente llamados "los posas") con los que hemos compartido más que un laboratorio, Inmunología (Mari, Bea, Mingui, Julia, Rosa, etc.), grandes amigos dentro y fuera de la UPF, y todos los demás grupos del departamento.Siguiendo la ampliación de espacio, gracias también a toda la gente del PRBB que han ayudado a que estos años se hicieran más amenos. Gracias a ellos se materializó viii la mejor terapia antiestrés, el voley, gracias a los Rabenessen de Caramel (incluido Iván, sí, podrás venir al pica pica de mi tesis, jeje).Gracias a mis compañeros de licenciatura, con ellos inicié este camino y espero seguir sendas cercanas a las suyas.A la gente del laboratorio de Paul Nurse en New York, gracias por haberme hecho pasar una de las m...

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Section: Some Of the Most Important Ones Arementioning

confidence: 99%

Promoter-driven splicing regulation in fission yeast

Moldón

Malapeira

Gabrielli

et al. 2008

Nature

135

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“…Using coimmunoprecipitation strategies, we and others recently reported that the EJC assembled in HeLa nuclear extract contains numerous epitopes, including those recognized by antibodies against REF/Aly, Y14, SRm160, DEK, RNPS1, UAP56, and Magoh (Blencowe et al 1998;Mayeda et al 1999;Kataoka et al 2000Kataoka et al , 2001Le Hir et al 2000a,b, 2001bMcGarvey et al 2000;Zhou et al 2000;Gatfield et al 2001;Luo et al 2001). When assembled in vivo, the EJC is additionally precipitated by antibodies against Upf2, Upf3, and the TAP:p15 heterodimer (Kim et al 2001b;Le Hir et al 2001a;Lykke-Andersen et al 2001). Finally, REF/Aly, Y14, SRm160, RNPS1, Upf2, Upf3, and TAP were all present in mRNPs immunopurified from the nuclear fraction of COS cells with antibodies against a subunit of the nuclear cap binding complex (Lejeune et al 2002).…”

mentioning

confidence: 99%

“…In higher eukaryotes, termination codons are recognized as premature if they occur upstream of at least one exon-exon junction. By marking the positions of exon-exon junctions, the EJC serves as a conduit for communication between the splicing, translational, and degradative machineries (Kim et al 2001b;Le Hir et al 2001a;Lykke-Andersen et al 2001). Finally, Magoh and Y14 (Mago Nashi and Tsunagi in Drosophila), form a tight heterodimer in vivo and are both required for the proper localization of oskar mRNA during Drosophila development (Hachet and Ephrussi 2001;Mohr et al 2001).…”

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confidence: 99%

5′ exon interactions within the human spliceosome establish a framework for exon junction complex structure and assembly

Reichert

Hir²,

Jurica³

et al. 2002

Genes Dev.

126

137

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A general consequence of pre-mRNA splicing is the stable deposition of several proteins 20-24 nucleotides (nt) upstream of exon-exon junctions on spliced mRNAs. This exon junction complex (EJC) contains factors involved in mRNA export, cytoplasmic localization, and nonsense-mediated mRNA decay. Here we probed the mechanism and timing of EJC assembly. Over the course of splicing, the 5 exon is subject to numerous dynamic protein-RNA interactions involving at least nine distinct polypeptides. Within the fully assembled spliceosome, these interactions afford protection to the last 25-27 nt of the 5 exon intermediate. Throughout their lifetimes in vivo, mRNAs exist as mRNA-protein particles (mRNPs). The associated proteins control every aspect of mRNA metabolism, from subcellular transport to translational efficiency to rate of decay. Exactly which proteins associate with a particular mRNA depends on its sequence, its subcellular localization, and its synthetic history. Furthermore, the complement of mRNP proteins evolves as the mRNA moves to different locations and is acted on by such processes as nuclear export and translation. Many proteins join the mRNP in the nucleus and then accompany it to the cytoplasm, where they influence subsequent mRNA metabolism ( These splicing-specific mRNP proteins constitute the exon junction complex (EJC), which associates with spliced mRNAs in a sequence-independent manner a fixed distance upstream of exon-exon junctions (Le Hir et al. 2000b). Using coimmunoprecipitation strategies, we and others recently reported that the EJC assembled in HeLa nuclear extract contains numerous epitopes, including those recognized by antibodies against REF/Aly, Y14, SRm160, DEK, RNPS1, UAP56, and Magoh (Blencowe et al. 1998;Mayeda et al. 1999;Kataoka et al. 2000Kataoka et al. , 2001Le Hir et al. 2000a,b, 2001bMcGarvey et al. 2000;Zhou et al. 2000;Gatfield et al. 2001;Luo et al. 2001). When assembled in vivo, the EJC is additionally precipitated by antibodies against Upf2, Upf3, and the TAP:p15 heterodimer (Kim et al. 2001b;Le Hir et al. 2001a;Lykke-Andersen et al. 2001). Finally, REF/Aly, Y14, SRm160, RNPS1, Upf2, Upf3, and TAP were all present in mRNPs immunopurified from the nuclear fraction of COS cells with antibodies against a subunit of the nuclear cap binding complex (Lejeune et al. 2002).The known EJC components function at multiple levels of mRNA metabolism. SRm160 and RNPS1 were originally characterized as activators of pre-mRNA splicing (Blencowe et al. 1998;Mayeda et al. 1999

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“…In addition, NMD usually requires termination to occur at least 50 nt upstream of the next exon-exon junction (14,17). Indeed in mammals, exon-exon junctions are ''marked'' by a multiprotein complex deposited on mRNA by the spliceosome and able to trigger NMD (18)(19)(20).…”

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confidence: 99%

RNA surveillance down-regulates expression of nonfunctional κ alleles and detects premature termination within the last κ exon

Delpy

Sirac

Magnoux

et al. 2004

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

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Random V(D)J junctions would generate nonfunctional and͞or out-of-frame sequences in about two-thirds of cases and result in abundant transcripts encoding truncated proteins. Although allelic exclusion at the DNA recombination level ensures that a single allele is functional, the frequent biallelic rearrangements need additional mechanisms to down-regulate aberrant transcripts in those cells with both a functionally and a nonfunctionally rearranged allele. The process of nonsense-mediated decay targets aberrantly rearranged Ig heavy-chain transcripts, but the situation of light-chain mRNAs is more complex, because they do not meet the usual requirements for nonsense-mediated decay and most often lack a spliceable intron downstream of the premature termination. We studied immunoglobulin heavy-chain ؊͞؊ pro-B cells in which light chain genes get rearranged and expressed in the absence of any selection for the assembly of a functional B cell receptor. Using this model, we show that the whole locus is accessible in pro-B cells and allows the assembly of a broad spectrum of V J segments, most of which are out-of-frame. This model provides an evaluation of the in vivo efficiency of RNA surveillance toward aberrant mRNAs produced in pro-B cells. Our data show that nonfunctional transcripts are excluded from the mature mRNA pool not only by detecting termination in an upstream exon but also by detecting changes in the position of termination within the last exon. Similar mechanisms efficiently down-regulate nonfunctional transcripts arising in normal mature B cells due to the biallelic transcription of rearranged genes. R andom deletions or additions at the Ig V(D)J junctions generate two-thirds of nonfunctional out-of-frame rearranged genes in B cell progenitors (1-3). Cell selection further allows the outgrowth of clones, each producing a single Ig selected for functionality and affinity for a non-self antigen determinant (4). Although some of those clones carry both functional and nonfunctional alleles of the immunoglobulin heavy-chain (IgH) and͞or light IgL loci, expression of truncated proteins is not observed in normal B cells, where aberrant transcripts are only present in very low amounts (5). For light chain (LC) genes, although the observed frequency of B cells carrying both a functional and a nonfunctional allele is Ͼ30% (1, 3), out-of-frame mature mRNA sequences were rarely obtained (6). Such an exclusion of nonfunctional Ig mRNA in B cells could involve transcriptional down-regulation and͞or mRNA quality control processes. Allelic asymmetry at the transcriptional level has been demonstrated for several cytokine genes (7,8). Concerning Ig genes, differences in the methylation status of alleles have been reported and correlated with an asymmetry in the replication pattern and the nuclear localization (9-10). However, transcriptional silencing of an excluded Ig gene allele has not been demonstrated, and, on the contrary, detection of rare out-of-frame transcripts in normal B cells indicates that this silencing...

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Communication of the Position of Exon-Exon Junctions to the mRNA Surveillance Machinery by the Protein RNPS1

Cited by 360 publications

References 29 publications

Promoter-driven splicing regulation in fission yeast

Promoter-driven splicing regulation in fission yeast

5′ exon interactions within the human spliceosome establish a framework for exon junction complex structure and assembly

RNA surveillance down-regulates expression of nonfunctional κ alleles and detects premature termination within the last κ exon

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