MRN1 implicates chromatin remodeling complexes and architectural factors in mRNA maturation.

MRN1 implicates chromatin remodeling complexes and architectural factors in mRNA maturation.
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DOI:
10.1371/journal.pone.0044373
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Holmberg S
Holmberg S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Düring L;Thorsen M;Petersen DS;Køster B;Jensen TH;Holmberg S

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染色质结构与mRNA加工事件之间存在函数关系,然而,到目前为止,只有几个相关因素得到了表征。在这里,我们发现缺乏染色质重塑因子RSC和染色质结构蛋白Nhp6A/Nhp6B功能的RSC nhp6突变体在限制性温度下积累含有内含子的Pre-ΔΔ。此外,我们还证明了RSC8-TS16nhp6ΔΔ细胞中存在低水平的U6SnRNA和U4/U6di-SnRNA,在限制性温度下生长两小时后,这种情况会进一步加剧。RSC8-TS16nhp6ΔΔ细胞中U6SnRNA和U4/U6di-SnRNA水平的这种变化表明存在剪接缺陷。我们鉴定MRN1(rsc nhp6ΔΔ的多拷贝抑制因子)是rsc nhp6ΔΔ合成病的生长抑制因子。MRN1是一种RNA结合蛋白,定位于细胞核和细胞质。观察到2微米-mrn1与剪接缺陷突变体Snt309Δ、prp3、prp4和prp22之间的遗传相互作用,以及额外的遗传分析链接mrn1、sNT309、NHP6A/B、SWI/snf和rsc,支持染色质结构在基因加工中的作用。
A functional relationship between chromatin structure and mRNA processing events has been suggested, however, so far only a few involved factors have been characterized. Here we show that rsc nhp6ΔΔ mutants, deficient for the function of the chromatin remodeling factor RSC and the chromatin architectural proteins Nhp6A/Nhp6B, accumulate intron-containing pre-mRNA at the restrictive temperature. In addition, we demonstrate that rsc8-ts16 nhp6ΔΔ cells contain low levels of U6 snRNA and U4/U6 di-snRNA that is further exacerbated after two hours growth at the restrictive temperature. This change in U6 snRNA and U4/U6 di-snRNA levels in rsc8-ts16 nhp6ΔΔ cells is indicative of splicing deficient conditions. We identify MRN1 (multi-copy suppressor of rsc nhp6ΔΔ) as a growth suppressor of rsc nhp6ΔΔ synthetic sickness. Mrn1 is an RNA binding protein that localizes both to the nucleus and cytoplasm. Genetic interactions are observed between 2 µm-MRN1 and the splicing deficient mutants snt309Δ, prp3, prp4, and prp22, and additional genetic analyses link MRN1, SNT309, NHP6A/B, SWI/SNF, and RSC supporting the notion of a role of chromatin structure in mRNA processing.
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