Identification of widespread ultra-edited human RNAs.

Identification of widespread ultra-edited human RNAs.

Blog Article

Adenosine-to-inosine modification of RNA molecules (A-to-I RNA editing) is an important mechanism that increases transciptome diversity.It occurs when a genomically encoded adenosine (A) is converted to an inosine (I) by ADAR proteins.Sequencing reactions read inosine as guanosine (G); therefore, current methods to detect A-to-I editing sites align RNA sequences to their corresponding DNA regions and identify A-to-G mismatches.However, such methods perform poorly on RNAs that underwent extensive editing ("ultra"-editing), Kitchen Tools as the large number of mismatches obscures the genomic origin of these RNAs.Therefore, only a few anecdotal ultra-edited RNAs have been discovered so far.

Here we introduce and apply a novel computational method to identify ultra-edited RNAs.We detected 760 ESTs containing 15,646 editing sites (more than 20 sites per EST, on average), of which 13,668 are novel.Ultra-edited RNAs exhibit the known sequence motif of ADARs and tend to localize in sense strand Alu elements.Compared to sites of mild editing, ultra-editing occurs primarily in Alu-rich regions, where potential base pairing with neighboring, inverted Alus creates particularly long double-stranded RNA structures.Ultra-editing sites are underrepresented in old Alu subfamilies, tend to be non-conserved, Me Spring Dress and avoid exons, suggesting that ultra-editing is usually deleterious.

A possible biological function of ultra-editing could be mediated by non-canonical splicing and cleavage of the RNA near the editing sites.