TRYPANOSOMA-BRUCEI SPLICED-LEADER RNA METHYLATIONS ARE REQUIRED FOR TRANSSPLICING INVIVO

被引:68
作者
MCNALLY, KP
AGABIAN, N
机构
[1] UNIV CALIF SAN FRANCISCO,INTERCAMPUS PROGRAM MOLEC PARASITOL,LAUREL HEIGHTS CAMPUS,SAN FRANCISCO,CA 94143
[2] UNIV CALIF BERKELEY,BERKELEY,CA 94720
关键词
D O I
10.1128/MCB.12.11.4844
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The TrYPanosoma brucei spliced leader (SL) RNA donates its 5' leader sequence to all nuclear pre-mRNAs via trans RNA splicing. The SL RNA is a small-nuclear U RNA-like molecule which is present in the cell as part of a small ribonucleoprotein particle. However, unlike the trimethylguanosine-capped small nuclear U RNAs, the SL RNA has a highly modified 5' terminus containing an m7G cap and methylations on the first four transcribed nucleotides. Here, we show that incubation of procyclic-form T. brucei in the presence of the S-adenosylmethionine analog, sinefungin, leads to a rapid inhibition of SL RNA methylation. A concomitant inhibition of trans splicing and an accumulation of high-molecular-weight tubulin transcripts were also observed. The effects of sinefungin on SL RNA methylation and on trans splicing were correlated by labeling of cells incubated in the presence of the antibiotic. The results indicate that 5' modifications of the SL RNA are necessary for it to participate in trans splicing. SL RNA modification is not required for assembly of the core SL ribonucleoprotein, as these Cs2SO4-resistant particles can be formed with either methylated or undermethylated SL RNA.
引用
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页码:4844 / 4851
页数:8
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