Innovating Works

lincSAFARI

Financiado
Sequence and Function Relationships in Long Intervening Noncoding RNAs
It is now clear that many intergenic regions in eukaryotic genomes give rise to a range of processed and regulated transcripts that do not appear to code for functional proteins. A subset of these are long (>200 nt), capped and po... It is now clear that many intergenic regions in eukaryotic genomes give rise to a range of processed and regulated transcripts that do not appear to code for functional proteins. A subset of these are long (>200 nt), capped and polyadenylated RNAs transcribed by RNA polymerase II and collectively called long intervening noncoding RNAs or lincRNAs. The recent estimates are that the human genome encodes >10,000 distinct lincRNAs, many of which show tissue-specific expression and are frequently dysregulated in human disease, including neurodegeneration. Given the growing number of lincRNAs implicated in human disease or required for proper development, fundamental questions that need to be addressed are: Which lincRNAs are functional? How is functional information encoded in the lincRNA sequence? Is this information interpreted in the context of the mature or the nascent RNA? What are the identities and functional roles of specific sequence domains within lincRNA genes? Our main hypothesis is that many lincRNA loci play key roles in gene regulation during cell differentiation, both via functionally important transcription events and post-transcriptionally, through the combined action of multiple short sequence domains. We will test this hypothesis using three complementary approaches – comparative genomics, detailed perturbations in mammalian cells followed by quantitative molecular phenotyping, and high-throughput screens for sequences able to carry out specific functions. We propose an interdisciplinary approach combining computational, molecular and stem cell biology. Our methodology will be scalable, allowing us to tackle completely uncharacterized long RNAs and eventually zoom in and study their individual bases. Upon successful accomplishment of the program, we will delineate modes of action of numerous lincRNAs, report sequence patches that are functionally important and understand how specific bases and structures act in concert to drive lincRNA function. ver más
31/05/2020
WEIZMANN
2M€
Duración del proyecto: 60 meses Fecha Inicio: 2015-05-11
Fecha Fin: 2020-05-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2020-05-31
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-StG-2014: ERC Starting Grant
Cerrada hace 10 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
WEIZMANN INSTITUTE OF SCIENCE No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5