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27 October 2008

Stanford researchers discover pervasive network driving protein production and placement in cells

Stanford researchers discover pervasive network driving protein production and placement in cells

"If you gaze into the genome, you see lots of regions that don't code for proteins but are conserved in nature - they remain unchanged from organism to organism over eons of evolutionary time," said Hogan. "This suggests that these regions may be playing some important regulatory role."

It's been known for some time that specialized regulatory proteins called transcription factors are able to enter the nucleus and recognize and bind to specific barcode-like sequences of nucleotides found on DNA. By occupying these sites, transcription factors can make it more or less likely that RNA copies of a specific gene will be produced. Because many genes scattered throughout the genome have identical nucleotide barcodes, transcription factors can simultaneously modulate the expression of entire batteries of widely spaced genes. Clusters of proteins with interdependent functions can be produced in a coordinate manner.

The Stanford investigators have discovered an analogous system of regulation instigated by a class of proteins that are distinguished by their binding not to DNA but to RNA. Scientists have long been aware of the existence of numerous proteins that bind RNA - an obvious example is the ubiquitous, protein-building molecular machines called ribosomes, which are themselves made largely of proteins. They also know that in isolated cases, RNA-binding proteins, or RBPs, seem to influence the fates of the RNA molecules to which they bind.

But few had suspected the global nature of such interactions, which the Stanford team has now revealed to guide the fate of most, if not all, protein-coding RNA molecules. The study showed that virtually every protein-coding RNA molecule encoded in the yeast genome appears to be bound by specific combinations of RBPs, which have been directed to their target RNAs by short, barcode-like sequences on those RNA molecules.

Equally significant was the group's discovery that, in many cases, individual RBPs associated with groups of RNAs that coded for proteins related either in function (they need to operate in close coordination with one another) or location (they do their jobs in the same part of the cell.) This is consistent with the notion that many RBPs guide their bound RNA molecules to particular locations in the cell, preventing intervention by ribosomes along the way and ensuring that a protein gets made in the right place at the right time.

"Our work suggests that what had seemed like a relatively few specialized RBPs that are involved in some specific regulatory processes instead constitute a pervasive system of biological regulation, in many ways paralleling that of transcription factors," said Brown. "Just as transcription factors are recruited to the specific sets of genes they regulate by recognizing specific DNA sequences, these RBPs are recruited to a specific set of RNAs they regulate by recognizing specific sequences in those RNA molecules." ...

"Here's this whole system - which has gone virtually unnoticed - that looks like it has a pervasive role in regulation," he said. "And we still know almost nothing about it. It looks like a great, unexplored area, which is just what you love if you're a scientist."

The Big Bang was an autotelic cosmic seed.

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