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Old 05-26-2003, 05:01 AM   #1
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Default Antisense RNAs are bad, mmkay?

Wonderful, warm and cuddly as so many new roles and applications for non coding RNAs are lets not forget the exciting new area they open up as the causes rather than the cures for disease.

Quote:
Nat Genet. 2003 May 5 (to be published)

Transcription of antisense RNA leading to gene silencing and methylation as anovel cause of human genetic disease.

Tufarelli C, Stanley JA, Garrick D, Sharpe JA, Ayyub H, Wood WG, Higgs DR.

Nearly all human genetic disorders result from a limited repertoire of mutations in an associated gene or its regulatory elements. We recently described an individual with an inherited form of anemia (alpha-thalassemia) who has a deletion that results in a truncated, widely expressed gene (LUC7L) becoming juxtaposed to a structurally normal alpha-globin gene (HBA2). Although it retains all of its local and remote cis-regulatory elements, expression of HBA2 is silenced and its CpG island becomes completely methylated early during development. Here we show that in the affected individual, in a transgenic model and in differentiating embryonic stem cells, transcription of antisense RNA mediates silencing and methylation of the associated CpG island. These findings identify a new mechanism underlying human genetic disease.
This is available online already at this adress
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Old 05-27-2003, 02:29 AM   #2
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Highness,
I didn't read the paper, since I'm supposed to be shirking work!
Just a thought though. Given that there is any number of RNA fragments floating around in the ER, and that motifs such as CpG islands, trinucleotide repeats and suchlike are fairly common, how would you rate the chances of random RNA-RNA hybridization in normal cellular biochemistry?
Would such a mechanism have any effect on post-transcriptional regulation of gene expression?
Amit
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Old 05-27-2003, 01:45 PM   #3
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I doubt that random hybridisation would have a particularly significant effect. Specific interactions between complementary RNA sequences certainly has .
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