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BFU2011-25697

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Cerrado

BASES MOLECULARES DEL SPLICING DE PRE-MRNA

DURING PRE-MRNA SPLICING MRNA IS SYNTHESIZED BY THE SPLICEOSOME, JOINING SEQUENTIAL PIECES (EXONS) AND DISCARDING OTHERS IN BETWEEN (INTRONS). IN MOST GENES THE SPLICEOSOME CAN MODULATE ITS CHOICES, ADAPTING THE FINAL MESSAGE TO T... ver más

01/01/2011

CSIC

247K€

Presupuesto del proyecto: 247K€

Líder del proyecto

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGA... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 2-3 | 552M€

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2011-01-01 No tenemos la información de la convocatoria

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Líder del proyecto

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGA... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 2-3 | 552M€

Presupuesto del proyecto 247K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto DURING PRE-MRNA SPLICING MRNA IS SYNTHESIZED BY THE SPLICEOSOME, JOINING SEQUENTIAL PIECES (EXONS) AND DISCARDING OTHERS IN BETWEEN (INTRONS). IN MOST GENES THE SPLICEOSOME CAN MODULATE ITS CHOICES, ADAPTING THE FINAL MESSAGE TO THE CELLS NEEDS (ALTERNATIVE SPLICING). THIS GREATLY AMPLIFIES THE CODING POTENTIAL OF GENOMES; AND ACCORDINGLY, THE SPLICEOSOME IS LIKELY TO BE THE MOST COMPLEX MOLECULAR MACHINE IN THE CELL. A FUNDAMENTAL PROBLEM IN THE FIELD IS IN OUR LACK OF UNDERSTANDING OF THE REGULATION OF MECHANISMS OF INTRON/EXON SELECTION BY THE SPLICEOSOME. THIS IS KEY TO SOLVE DISEASES ORIGINATED IN SPLICING DEFECTS. IT IS ALSO ESSENTIAL TO UNMASK THE GENETIC INFORMATION OF EUKARYOTIC GENOMES. SPLICING IS EVOLUTIONARILY CONSERVED AND ITS STUDY BENEFITS FROM THE WORK USING SEVERAL MODELS. THIS PROPOSAL IS BASED ON THE USE OF A SIMPLE SYSTEM, SUCH AS BUDDING YEAST, TO CONTRIBUTE TO OUR KNOWLEDGE OF REGULATED SPLICING. THE MAIN HYPOTHESIS, SUPPORTED BY AMPLE DATA, IS THAT THE YEAST SPLICEOSOME REPRESENTS A CORE VERSION OF THE HUMAN ONE. THEREFORE, IT CAN USED TO ASK HOW SPLICEOSOMAL FUNCTION CAN BE REGULATED AT THE LEVEL OF ITS BASIC COMPONENTS. SPECIFICALLY, THE PROPOSAL FOCUSES ON (1) WAYS OF MODULATING EARLY CONFORMATIONAL CHANGES THAT OCCUR DURING THE CO-TRANSCRIPTIONAL ASSEMBLY OF THE SPLICESOME; (2) SUBSTRATE RULES FOR THE SELECTION OF THE INTRONIC 3 END, INCLUDING THE POSSIBILITY THAT THE PRE-MRNA STRUCTURE CAN DIRECTLY CONTROL ALTERNATE CHOICES; (3) SEARCH OF NEW REGULATORY INTRONS, INCLUDING THOSE IN NON-CODING RNAS, THAT IS LIKELY TO PROVIDE NOVEL INSIGHTS INTO MECHANISMS OF REGULATION; AND (4) STUDY OF STRATEGIES OF REGULATION, PREVIOUSLY THOUGHT TO BE ABSENT IN YEAST, SUCH AS THOSE BASED ON THE PROCESSES OF EXON DEFINITION AND SPLICING SILENCERS/ENHANCERS. THESE OBJECTIVES ARE BASED ON PREVIOUS RESULTS FROM THE GROUP, AND OFFER THE USE OF A POWERFUL MODEL TO ADDRESS COMPLEX PROBLEMS RELEVANT TO THE WHOLE FIELD. THUS, TOGETHER WITH THE PROPOSED METHODOLOGY, THEY TAKE ADVANTAGE OF THE PARTICULARITIES OF YEAST, AND RELY ON TOOLS FROM BIOINFORMATICS, GENETICS, AND BIOCHEMISTRY RE-MRNA\EXON DEFINITION\INTRON DEFINITION\ESTRUCTURA RNA\LEVADURA\INTRON\SPLICING REGULATION

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