A microarray study of post-mortem mRNA degradation in mouse brain tissue.
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.


METHODS
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 h 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.


CONCLUSIONS
A subgroup of mammalian mRNA transcripts are particularly susceptible to PMI-related degradation, and as a group, they are more likely to carry the 3'UTR 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.
Catts
Vibeke Sørensen
VS
Queensland Brain Institute, University of Queensland, Brisbane QLD 4072, Australia.
Catts
Stanley Victor
SV
Fernandez
Harvey Robert
HR
Taylor
Jennifer Maree
JM
Coulson
Elizabeth Jane
EJ
Lutze-Mann
Louise Helen
LH
D020413:3' Untranslated Regions / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011180:Postmortem Changes; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors
D020413:3' Untranslated Regions; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger