Abstract
Even though proteins are produced from mRNA, the correlation between mRNA levels and protein abundances is moderate in most studies, occasionally attributed to complex post-transcriptional regulation. To address this, we generate a paired transcriptome/proteome time course dataset with 14 time points during Drosophila embryogenesis. Despite a limited mRNA-protein correlation (ρ = 0.54), mathematical models describing protein translation and degradation explain 84% of protein time-courses based on the measured mRNA dynamics without assuming complex post transcriptional regulation, and allow for classification of most proteins into four distinct regulatory scenarios. By performing an in-depth characterization of the putatively post-transcriptionally regulated genes, we postulate that the RNA-binding protein Hrb98DE is involved in post-transcriptional control of sugar metabolism in early embryogenesis and partially validate this hypothesis using Hrb98DE knockdown. In summary, we present a systems biology framework for the identification of post-transcriptional gene regulation from large-scale, time-resolved transcriptome and proteome data.
Highlights
StationarDyegradationPrDoedluacyteiodn-production RejeHcrtbe9d8DE target c d b3Protein change only (26) mRNA change only (217)Spearman correlation 0.35Log[2] fold-change mRNA emRNA R1 mRNA R2 mRNA R3 Protein R1 Protein R2 Protein R3 Protein R4 % genes mRNA and protein changeRegulation of glucose metabolismDifferentially spliced genes in S2R+ data 118Protein change only 852 No changeHrb98DE target genes
Compared to the previous modeling studies, we describe a framework for the systematic discovery of posttranscriptional regulation mechanisms controlling a biological process of interest: We combine model fitting and model rejection to explicitly name mRNA−protein pairs insufficiently described by four distinct model variants, thereby deriving lists of potentially post-transcriptionally regulated proteins
We considered 67 Drosophila-specific RNA -binding protein (RBP) motifs corresponding to 51 different RBPs37
Summary
StationarDyegradationPrDoedluacyteiodn-production RejeHcrtbe9d8DE target c d b3Protein change only (26) mRNA change only (217)Spearman correlation 0.35Log[2] fold-change mRNA emRNA R1 mRNA R2 mRNA R3 Protein R1 Protein R2 Protein R3 Protein R4 % genes mRNA and protein changeRegulation of glucose metabolismDifferentially spliced genes in S2R+ data 118Protein change only 852 No changeHrb98DE target genes. Protein change only (26) mRNA change only (217). Log[2] fold-change mRNA e. MRNA R1 mRNA R2 mRNA R3 Protein R1 Protein R2 Protein R3 Protein R4 % genes mRNA and protein change.
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