U1 snRNP telescripting regulates a size-function-stratified human genome.
Nat Struct Mol Biol
; 24(11): 993-999, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-28967884
ABSTRACT
U1 snRNP (U1) functions in splicing introns and telescripting, which suppresses premature cleavage and polyadenylation (PCPA). Using U1 inhibition in human cells, we show that U1 telescripting is selectively required for sustaining long-distance transcription elongation in introns of large genes (median 39 kb). Evidence of widespread PCPA in the same locations in normal tissues reveals that large genes incur natural transcription attrition. Underscoring the importance of U1 telescripting as a gene-size-based mRNA-regulation mechanism, small genes were not sensitive to PCPA, and the spliced-mRNA productivity of â¼1,000 small genes (median 6.8 kb) increased upon U1 inhibition. Notably, these small, upregulated genes were enriched in functions related to acute stimuli and cell-survival response, whereas genes subject to PCPA were enriched in cell-cycle progression and developmental functions. This gene size-function polarization increased in metazoan evolution by enormous intron expansion. We propose that telescripting adds an overarching layer of regulation to size-function-stratified genomes, leveraged by selective intron expansion to rapidly shift gene expression priorities.
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Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Genoma Humano
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Regulação da Expressão Gênica
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Ribonucleoproteína Nuclear Pequena U1
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Poliadenilação
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article