A microarray study of post-mortem mRNA degradation in mouse brain tissue
A microarray study of post-mortem mRNA degradation in mouse brain tissue
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DOI：
10.1016/j.molbrainres.2005.04.017
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发表时间：
2005-08-18
期刊：
影响因子：
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通讯作者：
Lutze-Mann, LH
中科院分区：
文献类型：
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作者：
Catts, VS;Catts, SV;Lutze-Mann, LH
背景资料：虽然有证据表明，死后间隔（PMI）是不是一个主要的贡献者减少整体RNA的完整性，它可能会有差异地影响一个亚组的基因转录物，容易受到PMI相关的降解。方法：成年小鼠死后0，6，12，18，24，36和48 h取脑组织。通过将来自零时间点的RNA与来自每个PMI时间点的测试RNA杂交来测量RNA转录物丰度，并使用cDNA微阵列评估差异基因表达。序列和本体论分析上进行的RNA转录组显示大于2倍reduction.Results：增加PMI与降低组织pH值和增加RNA降解的28 S/18 S核糖体RNA的比例为指标。在阵列上检测到的大约12%的mRNA在死后48小时显示出超过两倍的丰度下降。核苷酸组成分析提供的证据表明，与不携带3 'UTR AUUUA基序的转录物相比，在3'非翻译区（3 'UTR）中具有AUUUA基序的转录物更容易受到PMI相关RNA降解的影响。与这一发现相一致，本体分析表明，转录因子和元件被过度代表在组的成绩单易degradation.Conclusion：一个亚组的哺乳动物mRNA转录本是特别容易受到PMI相关的降解，作为一个群体，他们更有可能携带的YUTR AUUUA基序。在人类和动物模型死后脑研究中，尤其是那些包括广谱mRNA转录物的研究中，应控制PMI。(c)2005 Elsevier B. V.保留所有权利。
Background: Although there is evidence that post-mortem interval (PMI) is not a major contributor to reduced overall RNA integrity, it may differentially affect a subgroup of gene transcripts that are susceptible to PMI-related degradation. This would particularly have ramifications for microarray studies that include a broad spectrum of genes.Method: Brain tissue was removed from adult mice at 0, 6, 12, 18, 24,36 and 48 h post-mortem. RNA transcript abundance was measured by hybridising RNA from the zero time point with test RNA from each PMI time point, and differential gene expression was assessed using cDNA microarrays. Sequence and ontological analyses were performed on the group of RNA transcripts showing greater than two-fold reduction.Results: Increasing PMI was associated with decreased tissue pH and increased RNA degradation as indexed by 28S/18S ribosomal RNA ratio. Approximately 12% of mRNAs detected on the arrays displayed more than a two-fold decrease in abundance by 48 It post-mortem. An analysis of nucleotide composition provided evidence that transcripts with the AUUUA motif in the 3' untranslated region (3'UTR) were more susceptible to PMI-related RNA degradation, compared to transcripts not carrying the 3'UTR AUUUA motif. Consistent with this finding, ontological analysis showed transcription factors and elements to be over-represented in the group of transcripts susceptible to degradation.Conclusion: A subgroup of mammalian mRNA transcripts are particularly susceptible to PMI-related degradation, and as a group, they are more likely to carry the YUTR AUUUA motif. PMI should be controlled for in human and animal model post-mortem brain studies, particularly those including a broad spectrum of mRNA transcripts. (c) 2005 Elsevier B.V. All rights reserved.