Mg. Hamshere et al., TRANSCRIPTIONAL ABNORMALITY IN MYOTONIC-DYSTROPHY AFFECTS DMPK BUT NOT NEIGHBORING GENES, Proceedings of the National Academy of Sciences of the United Statesof America, 94(14), 1997, pp. 7394-7399
Myotonic dystrophy (DM) is caused by the expansion of a trinucleotide
repeat, CTG, in the 3' untranslated region of a protein kinase gene, D
MPK. We set out to determine what effect this expanded repeat has on R
NA processing. The subcellular fractionation of RNA and the separate a
nalysis of DMPK transcripts from each allele reveals that transcripts
from expanded DMPK alleles are retained within the nucleus and are abs
ent from the cytoplasm of DM cell lines. The nuclear retention of DMPK
transcripts occurs above a critical threshold between 80 and 400 CTGs
. Further analysis of the nuclear RNA reveals an apparent reduction in
the proportion of expansion-derived DMPK transcripts after poly(A)(+)
selection. Quantitative analysis of RNA also indicates that although
the level of cytoplasmic DMPK transcript is altered in DM patients, th
e levels of transcripts from 59 and DMAHP, two genes that immediately
flank DMPK, are unaffected in DM cell lines.