Paiva Marcelo M, Kimura Edna T, Coltri Patricia P
Department of Cell and Developmental Biology, Institute for Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Department of Cell and Developmental Biology, Institute for Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
Cancer Genomics Proteomics. 2017 Sep-Oct;14(5):373-381. doi: 10.21873/cgp.20047.
Thyroid cancer is one of the most frequent types of endocrine cancers. In most cases, thyroid cancers are caused by deregulated miRNA expression, especially involving the miR17-92 cluster. miR17-92 transcription is altered in several different tumor types including lymphoma, leukemia, and of the breast and thyroid. As an intronic cluster, miR17-92 must be processed during splicing and therefore interaction between microprocessor and spliceosome machineries is of major importance in understanding its expression.
We investigated the protein composition of spliceosomes assembled on pre-RNAs containing intronic miR18a and miR19a, components of the miR17-92 cluster, using mass spectrometry.
Interestingly, we observed that proteins associated with intronic miR18a and miR19a are cell-specific, and are similar for both miRNAs analyzed. The only exception is the group of heterogeneous nuclear proteins that are commonly recruited by different cells.
miRNA processing depends on cell-specific proteins and heterogeneous nuclear proteins have a general role in miRNA processing from introns.
甲状腺癌是最常见的内分泌癌类型之一。在大多数情况下,甲状腺癌是由miRNA表达失调引起的,尤其是涉及miR17 - 92簇。miR17 - 92的转录在包括淋巴瘤、白血病以及乳腺癌和甲状腺癌在内的几种不同肿瘤类型中发生改变。作为一个内含子簇,miR17 - 92在剪接过程中必须被加工,因此微处理器和剪接体机制之间的相互作用对于理解其表达至关重要。
我们使用质谱法研究了在含有内含子miR18a和miR19a(miR17 - 92簇的组成部分)的前体RNA上组装的剪接体的蛋白质组成。
有趣的是,我们观察到与内含子miR18a和miR19a相关的蛋白质具有细胞特异性,并且对于所分析的两种miRNA来说是相似的。唯一的例外是不同细胞通常都会招募的异质性核蛋白组。
miRNA加工依赖于细胞特异性蛋白质,而异质性核蛋白在从内含子进行miRNA加工中具有普遍作用。