DNA Needs a Good Editor: Researchers Unravel the Mysteries of DNA Packaging
ScienceDaily (Dec. 15, 2009) — Imagine a huge spool of film containing thousands of sequences of random scenes. Without a talented editor, a screening would have no meaning.
The RNA "spools" that make up DNA in our genes need careful editing, too. Genes are composed of meaningful sequences, called exons, separated by meaningless junk sections called introns. In order for cells to produce RNA -- the material that is required to create proteins that are vital for life -- they must precisely remove meaningless introns and bind meaningful exons together, a process called "splicing."
How cells differentiate between what's useful and what's garbage in our complicated and messy genetic code is a fundamental biology question -- one with extremely important implications. Now, Prof. Gil Ast and his doctoral student Schraga Schwartz at the Sackler School of Medicine at Tel Aviv University are successfully finding answers.
Their groundbreaking findings, recently published in Nature Structural and Molecular Biology, reveal a new mechanism to explain how splicing works. They've discovered that the structure of DNA itself affects the ways RNA is spliced. "These findings," says Prof. Ast, "will bring us closer to understanding diseases like cystic fibrosis and certain forms of cancer that result from our cells' failure to edit sequences properly."
Rewriting textbook science on DNA
Until now, how RNA was "edited" to fit together has been a mystery. The TAU revelations provide important information about creating proteins, and give new clues to drug developers to better understand how diseases such as cancer and genetic disorders operate at the gene level. That insight can offer significant new cellular mechanisms to create innovative drug therapies.
"We've found something previously unknown," Prof. Ast explains. "At the DNA level, exons are packaged differently than introns. This fact is significant, telling us a process of gene expression is taking place at an earlier step than previously believed." This can give new clues to scientists seeking to detect and diagnose diseases before they erupt, he believes.
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Analysis abstract
Nature Structural & Molecular Biology 16, 990 - 995 (2009)
Published online: 16 August 2009 | doi:10.1038/nsmb.1659
Chromatin organization marks exon-intron structure
Schraga Schwartz1, Eran Meshorer2 & Gil Ast1
Abstract
An increasing body of evidence indicates that transcription and splicing are coupled, and it is accepted that chromatin organization regulates transcription. Little is known about the cross-talk between chromatin structure and exon-intron architecture. By analysis of genome-wide nucleosome-positioning data sets from humans, flies and worms, we found that exons show increased nucleosome-occupancy levels with respect to introns, a finding that we link to differential GC content and nucleosome-disfavoring elements between exons and introns. Analysis of genome-wide chromatin immunoprecipitation data in humans and mice revealed four specific post-translational histone modifications enriched in exons. Our findings indicate that previously described enrichment of H3K36me3 modifications in exons reflects a more fundamental phenomenon, namely increased nucleosome occupancy along exons. Our results suggest an RNA polymerase II–mediated cross-talk between chromatin structure and exon-intron architecture, implying that exon selection may be modulated by chromatin structure.
1. Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.
2. Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, Israel.
Correspondence to: Gil Ast1 e-mail: gilast@post.tau.ac.il
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NOTA DESTE BLOGGER:
A cada dia que vejo pesquisas científicas assim, mais me convenço da robustez científica da teoria do Design Inteligente no contexto de justificação teórica.