Unknown

Dataset Information

0

NMR structure of an alpha-L-LNA:RNA hybrid: structural implications for RNase H recognition.


ABSTRACT: Alpha-L-LNA (alpha-L-ribo configured locked nucleic acid) is a nucleotide analogue that raises the thermostability of nucleic acid duplexes by up to approximately 4 degrees C per inclusion. We have determined the NMR structure of a nonamer alpha-L-LNA:RNA hybrid with three alpha-L-LNA modifications. The geometry of this hybrid is intermediate between A- and B-type, all nucleobases partake in Watson-Crick base pairing and base stacking, and the global structure is very similar to that of the corresponding unmodified hybrid. The sugar-phosphate backbone is rearranged in the vicinity of the modified nucleotides. As a consequence, the phosphate groups following the modified nucleotides are rotated into the minor groove. It is interesting that the alpha-L-LNA:RNA hybrid, which has an elevation in melting temperature of 17 degrees C relative to the corresponding DNA:RNA hybrid, retains the global structure of this hybrid. To our knowledge, this is the first example of such a substantial increase in melting temperature of a nucleic acid analogue that does not act as an N-type (RNA) mimic. alpha-L-LNA:RNA hybrids are recognised by RNase H with subsequent cleavage of the RNA strand, albeit with slow rates. We attempt to rationalise this impaired enzyme activity from the rearrangement of the sugar-phosphate backbone of the alpha-L-LNA:RNA hybrid.

SUBMITTER: Nielsen JT 

PROVIDER: S-EPMC219478 | BioStudies | 2003-01-01

REPOSITORIES: biostudies

Similar Datasets

2012-01-01 | S-EPMC3499693 | BioStudies
2008-01-01 | S-EPMC2275159 | BioStudies
2006-01-01 | S-EPMC1435981 | BioStudies
2018-01-01 | S-EPMC5733572 | BioStudies
2001-01-01 | S-EPMC1221678 | BioStudies
2020-01-01 | S-EPMC7754139 | BioStudies
| S-EPMC283519 | BioStudies
2012-01-01 | S-EPMC3361345 | BioStudies
2020-01-01 | S-EPMC7764398 | BioStudies
2003-01-01 | S-EPMC218706 | BioStudies