Pedal to the Metal: Nuclear Splicing Bodies Turbo-Charge VSG mRNA Production in African Trypanosomes.
Pedal to the Metal: Nuclear Splicing Bodies Turbo-Charge VSG mRNA Production in African Trypanosomes.
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DOI：
10.3389/fcell.2022.876701
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发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
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非洲布鲁氏锥虫是哺乳动物血液和组织中的一种寄生虫，其抗原可变的变表面糖蛋白（VSG）外壳保护它免受免疫攻击。这一致密层由~ 107个VSG蛋白组成，使VSG成为锥虫血流中最丰富的mRNA（总数7-10%）和蛋白质（总数约10%）。一个VSG基因是如何产生如此大量的VSG的？活性VSG极高水平的RNA聚合酶I （Pol I）转录提供了部分解释。然而，最近的发现强调了前mrna加工的作用，既维持高水平的VSG转录，也维持其单等位基因的表达。锥虫mrna的成熟是通过将一个剪接的前体转录本的5 '端进行反式剪接来实现的，这意味着整个细胞核中需要大量的SL RNA。然而，活性VSG基因附近对SL RNA的需求是如此强烈，以至于细胞重新配置其染色质结构以促进SL RNA基因与活性VSG之间的相互作用。这可能确保了足够的局部SL RNA可用，而不限制VSG mRNA的表达。最近，新的核剪接体似乎提供必要的反式剪接成分，已被确定与活性VSG相关。这些观察结果强调了前mrna加工在调节锥虫基因表达中的作用。解剖这些核RNA加工体的功能将有助于我们阐明布鲁氏体中VSG表达和单等位基因排斥的机制。
The African trypanosome Trypanosoma brucei is a parasite of the mammalian bloodstream and tissues, where an antigenically variable Variant Surface Glycoprotein (VSG) coat protects it from immune attack. This dense layer comprised of ∼107 VSG proteins, makes VSG by far the most abundant mRNA (7–10% total) and protein (∼10% total) in the bloodstream form trypanosome. How can such prodigious amounts of VSG be produced from a single VSG gene? Extremely high levels of RNA polymerase I (Pol I) transcription of the active VSG provide part of the explanation. However, recent discoveries highlight the role of pre-mRNA processing, both in maintaining high levels of VSG transcription, as well as its monoallelic expression. Trypanosome mRNAs are matured through trans-splicing a spliced leader (SL) RNA to the 5’ end of precursor transcripts, meaning abundant SL RNA is required throughout the nucleus. However, requirement for SL RNA in the vicinity of the active VSG gene is so intense, that the cell reconfigures its chromatin architecture to facilitate interaction between the SL RNA genes and the active VSG. This presumably ensures that sufficient localised SL RNA is available, and not limiting for VSG mRNA expression. Recently, novel nuclear splicing bodies which appear to provide essential trans-splicing components, have been identified associating with the active VSG. These observations highlight the underappreciated role of pre-mRNA processing in modulating gene expression in trypanosomes. Dissecting the function of these nuclear RNA processing bodies should help us elucidate the mechanisms of both VSG expression and monoallelic exclusion in T. brucei.
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影响因子：
14.9
作者：
Rothé B;Back R;Quinternet M;Bizarro J;Robert MC;Blaud M;Romier C;Manival X;Charpentier B;Bertrand E;Branlant C
通讯作者：
Branlant C
影响因子：
16.6
作者：
Faria, Joana;Glover, Lucy;Horn, David
通讯作者：
Horn, David
DOI：
10.1073/pnas.1600344113
发表时间：
2016-06-28
影响因子：
11.1
作者：
Glover, Lucy;Hutchinson, Sebastian;Horn, David
通讯作者：
Horn, David
影响因子：
11.4
作者：
Chaves, I;Rudenko, G;Borst, P
通讯作者：
Borst, P
DOI：
10.1073/pnas.82.3.722
发表时间：
1985-01-01
影响因子：
11.1
作者：
GRUMMT, I;SKINNER, JA
通讯作者：
SKINNER, JA