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As I understand it, the splicing of introns from pre-mRNAs is not incredibly precise. I've only ever seen nucleotide position ranges given in any description of the involved processes. Since there is quite a bit of looping of pre-mRNAs during processing and given that involved proteins often have effects well downstream from where they bind, this intuitively makes sense.

However, this would be incredibly problematic if true. Most pre-mRNAs are more intron than they are exon. While the precise base offset for the bases padding the start and end of an mRNA are irrelevant due to the start and stop codons, the precise offset for cut locations is very important for any splicing between the start and stop codons. If the splicing of introns regularly lead to cuts that are 1 or 2 bases off (in addition to 0 or more whole codons that have been accidentally removed), then all eukaryotic cells should have lots of (junk) mature mRNAs that have the proper reading frame at their 5' ends but off frame codons at the 3' end or just for stretches in the middle.

Specifically, if pre-mRNA processing has mostly random cut locations in its splicing, I would expect only ${^1/_3}^{rd}$ of mRNAs to retain the reading frame of their parent genes from from start to poly-A. In turn, that would mean only about ${^1/_3}^{rd}$ of synthesized proteins have the proper primary structure. There's no way eukaryotes function with that much kludge running through them.

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    $\begingroup$ "the splicing of introns from pre-mRNAs is not incredibly precise.".. Why would you suppose so? Do you have any reference to support this? AFAIK, splicing is decently precise in cases where precision is needed (when there is no alternate splicing involved). However, there can be such frameshifts but since they are not detected with decent coverage in RNAseq experiments, we can assume that such missplicing events are not significantly frequent. $\endgroup$ – WYSIWYG Dec 23 '16 at 6:31
  • $\begingroup$ As noted in the comment above, our understanding is that splicing is generally quite precise. Keep in mind also that if you do get a splice error, you have a very high probability of introducing a premature stop codon, which, among other things, will mean that the rest of the mRNA is not translated and is likely to be degraded. $\endgroup$ – Victor Chubukov Dec 23 '16 at 21:15

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