These promoter-associated small RNAs, or PASRs, can be contrasted with a new species just discovered by Gingeras, Hannon and colleagues, a type they call non-PASRs. The latter originate at sites distant from those where PASRs are generated. Both types of small RNAs were observed to have undergone "capping," a chemical modification that makes them stable and impervious to degradation. "This quality," Hannon observes, "lengthens their lifespan in the cell, a clue that suggests these small RNA classes may have significant biological duties."
Curiously, PASRs and non-PASRs may not be initially synthesized in their "short" form. The CSHL team proposes a model in which mature long RNAs are cleaved followed by a capping of the newly generated long RNA fragment. This is followed by the clipping of the end of the capped long RNA to produce a short RNA product.
Small RNAs can act as "off" switches at "on" sites
Now that these new capped small RNA types have been discovered, the question naturally arises: what do they do? Using a human gene called MYC as a model, the team studied how the presence of PASRs at the start site of a gene impacted its expression, i.e., the way it manifested itself in a living cell. The researchers found that if the level of expression of PASRs was increased, the expression of the MYC gene was reduced. PASRs thus seem to modulate the production of mature RNA transcripts.
The function of non-PASRs is unclear at the moment. This class of RNAs "could possibly participate more globally in a bookkeeping or quality-control mechanism by which the cell keeps track of the genes it is expressing -- its transcriptional output," according to Gingeras.
This work and the future contributions of the ENCODE project have a larger significance in understanding the genetic roots of human disease. "Unless we obtain much more information about non-protein coding sequences of the genome and learn how various functional elements in the genome impact the production of proteins, we won't fully be able to understand the biological and clinical effects of disease-causing mutations," Gingeras emphasizes.
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