Molecular Biology

Choosing Your 3' End

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Science  30 Sep 2011:
Vol. 333, Issue 6051, pp. 1802-1803
DOI: 10.1126/science.333.6051.1802-d

Many eukaryotic genes contain noncoding sequences—introns—that must be removed before translation. The 5' slice site is determined by base-pairing interactions with the U1 snRNA of the spliceosome, a large ribonuclear-protein complex that catalyses the removal of introns. How the spliceosome finds the other (3') end of the intron—nominally marked by no more than the dinucleotide sequence AG—is less clear.

While studying a budding yeast gene, Meyer et al. found that the potential destabilization of an RNA secondary structure downstream of the intron branch point (a sequence critical in the splicing reaction) had an adverse effect on splicing. Analyzing the RNA folding potential of sequences between the intron branch point and the 3' splice site for 282 yeast introns revealed that a substantial fraction had the potential to form secondary structures. In vivo, the RNA secondary structure functioned to bring distant 3' splice sites within a specific distance window, which is neither too close to nor too far from the intron branch point, thus allowing effective 3' splicing to occur and implying that the spliceosome has a limited “reach.” For another gene, choice of the 3' splice site is infl uenced by temperature, which is sensed through the thermal stability of the RNA secondary structure, implying that such structures can function in a regulatory capacity.

Mol. Cell 43, 1033 (2011).

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