Extensive gene-specific translational reprogramming in a model of B cell differentiation and Abl-dependent transformation.
Extensive gene-specific translational reprogramming in a model of B cell differentiation and Abl-dependent transformation.
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DOI：
10.1371/journal.pone.0037108
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Brown PO
中科院分区：
文献类型：
--
作者：
Bates JG;Salzman J;May D;Garcia PB;Hogan GJ;McIntosh M;Schlissel MS;Brown PO
翻译的调控在多大程度上可能有助于分化程序或癌症的分子发病机制？用病毒致癌基因v-Abl转化的前b细胞悬浮在一种永生化的循环状态中，这种状态模仿了BCR-ABL1易位的白血病，如慢性髓性白血病（CML）和急性淋巴细胞白血病（ALL）。用伊马替尼抑制致癌Abl激酶逆转转化，允许进展到B细胞发育的下一个阶段。我们采用了一种称为梯度编码的全基因组多体分析方法来研究v- abl转化的前b细胞的转化和分化的翻译调节程度和潜在贡献。超过一半的显著翻译调控基因在mRNA丰度水平上没有显著变化，揭示了通过单独测量转录物丰度变化可能错过的生物学。我们发现翻译中广泛的、基因特异性的变化影响了已知在B细胞信号传导和分化、癌性转化和细胞骨架重组中起作用的基因，这些基因可能影响粘附。这些结果强调了基因特异性翻译调控在分化和恶性转化过程中重塑基因表达程序的重要作用。
To what extent might the regulation of translation contribute to differentiation programs, or to the molecular pathogenesis of cancer? Pre-B cells transformed with the viral oncogene v-Abl are suspended in an immortalized, cycling state that mimics leukemias with a BCR-ABL1 translocation, such as Chronic Myelogenous Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL). Inhibition of the oncogenic Abl kinase with imatinib reverses transformation, allowing progression to the next stage of B cell development. We employed a genome-wide polysome profiling assay called Gradient Encoding to investigate the extent and potential contribution of translational regulation to transformation and differentiation in v-Abl-transformed pre-B cells. Over half of the significantly translationally regulated genes did not change significantly at the level of mRNA abundance, revealing biology that might have been missed by measuring changes in transcript abundance alone. We found extensive, gene-specific changes in translation affecting genes with known roles in B cell signaling and differentiation, cancerous transformation, and cytoskeletal reorganization potentially affecting adhesion. These results highlight a major role for gene-specific translational regulation in remodeling the gene expression program in differentiation and malignant transformation.
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