Genomic analysis suggests that mRNA destabilization by the microprocessor is specialized for the auto-regulation of Dgcr8.
Genomic analysis suggests that mRNA destabilization by the microprocessor is specialized for the auto-regulation of Dgcr8.
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DOI：
10.1371/journal.pone.0006971
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发表时间：
2009-09-11
期刊：
影响因子：
3.7
通讯作者：
Blelloch R
中科院分区：
文献类型：
--
作者：
Shenoy A;Blelloch R
微处理器包含RNA结合蛋白Dgcr8和RNase III酶Drosha，负责将初级microRNA处理为前体microRNA。微处理器通过切割Dgcr 8 mRNA的5′UTR和编码区中的发夹来调节自身水平，从而使成熟转录物不稳定。为了确定微处理器是否在直接调节其他编码mRNA水平方面具有更广泛的作用，我们整合了小RNA的表达谱和超高通量深度测序的结果。野生型、Dgcr8敲除和Dicer敲除小鼠胚胎干（ES）细胞中mRNA的表达分析揭示了在Dgcr8无效背景中特异性上调的mRNA。这些转录本中的许多具有微处理器的进化上保守的预测发夹靶。然而，对小鼠ES、HeLa和HepG2中18至200 nt小RNA的深度测序数据的分析表明，以与微处理器活性一致的模式映射的外显子序列读段是Dgcr8所独有的。我们的结论是，微处理器的作用，直接不稳定的编码mRNA可能是专门针对Dgcr8本身，这表明一个专门的细胞机制的基因自动调节。
The Microprocessor, containing the RNA binding protein Dgcr8 and RNase III enzyme Drosha, is responsible for processing primary microRNAs to precursor microRNAs. The Microprocessor regulates its own levels by cleaving hairpins in the 5′UTR and coding region of the Dgcr8 mRNA, thereby destabilizing the mature transcript. To determine whether the Microprocessor has a broader role in directly regulating other coding mRNA levels, we integrated results from expression profiling and ultra high-throughput deep sequencing of small RNAs. Expression analysis of mRNAs in wild-type, Dgcr8 knockout, and Dicer knockout mouse embryonic stem (ES) cells uncovered mRNAs that were specifically upregulated in the Dgcr8 null background. A number of these transcripts had evolutionarily conserved predicted hairpin targets for the Microprocessor. However, analysis of deep sequencing data of 18 to 200nt small RNAs in mouse ES, HeLa, and HepG2 indicates that exonic sequence reads that map in a pattern consistent with Microprocessor activity are unique to Dgcr8. We conclude that the Microprocessor's role in directly destabilizing coding mRNAs is likely specifically targeted to Dgcr8 itself, suggesting a specialized cellular mechanism for gene auto-regulation.
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