Actually, it remains possible that there are trimeric or even tetrameric RNAs, each of which contains sequences from three or four genes, respectively, although until now their existence is only suggested by many expression sequence tags (ESTs), but not by conclusive experimental evidence. For instance, while each RNA in any of the abovementioned four categories is derived from a single gene on a chromosome, there are so-called “chimeric RNAs” (herein “chimeras”), which defines those RNAs containing sequences of two genes. However, RNAs can also be classified by other criteria. One of us has recently proposed that noncoding RNAs, which can be processed from RNAs transcribed by either one of the three RNA polymerases, should be considered as the fourth category.
In today’s chimeric RNA research, there are still several key flaws, technical constraints and understudied tasks, which are also described in this perspective essay.Ĭlassically, mature RNAs in eukaryotic cells are categorized as ribosomal RNAs (rRNAs), messenger RNAs (mRNAs) and transfer RNAs (tRNAs), which are synthesized by RNA polymerases I, II and III, respectively. Many RNAs containing sequences of two neighboring genes may be transcribed via a readthrough mechanism, and thus are actually RNAs of unannotated genes or RNA variants of known genes, but not chimeras. We propose that only those RNAs that are formed by joining two RNA transcripts together without a fusion gene as a genomic basis should be regarded as authentic chimeras, whereas those RNAs transcribed as, and cis-spliced from, single transcripts should not be deemed as chimeras. Otherwise, not only will chimeric RNA studies be misled but also characterization of fusion genes and unannotated genes will be hindered. Since the number of putative chimeras is soaring, it is imperative to establish a pellucid definition for it, in order to differentiate chimeras from regular RNAs. However, “chimeric RNA” has never been lucidly defined, partly because “gene” itself is still ill-defined and because the means of production for many RNAs is unclear. There have been tens of thousands of RNAs deposited in different databases that contain sequences of two genes and are coined chimeric RNAs, or chimeras.
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