Dataset Information

On the relationship of protein and mRNA dynamics in vertebrate embryonic development

ABSTRACT: How the fertilized egg develops the anatomy of an adult ultimately must be explained at the biochemical level. Deeply connected to the anatomy is the complement of proteins and RNAs expressed during embryogenesis. The relationship of mRNA and respective protein expression dynamics during development has never been systematically explored. Here we present a comprehensive characterization of protein and mRNA dynamics across early development in Xenopus, between unfertilized egg and early tadpole stage. Surprisingly, most proteins change very little; there is an inverse correlation between abundance and rate of change. While the correlation of mRNA and protein expression is poor, a simple mass action kinetics model connects protein to RNA. Parameterized by two fixed parameters the median protein synthesis and degradation rates, the model depends on RNA dynamics, and initial protein concentration. Associated mRNA datasets in GEO: GSE73905 and GSE73870.

OTHER RELATED OMICS DATASETS IN: PRJNA298254PRJNA298391PRJNA298393

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Xenopus Laevis (african Clawed Frog)

TISSUE(S): Embryo

SUBMITTER: Martin Wuehr

LAB HEAD: Steven Gygi

PROVIDER: PXD002349 | Pride | 2015-10-20

REPOSITORIES: Pride

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Publications

On the Relationship of Protein and mRNA Dynamics in Vertebrate Embryonic Development.

Peshkin Leonid L Wühr Martin M Pearl Esther E Haas Wilhelm W Freeman Robert M RM Gerhart John C JC Klein Allon M AM Horb Marko M Gygi Steven P SP Kirschner Marc W MW

Developmental cell 20151101 3

A biochemical explanation of development from the fertilized egg to the adult requires an understanding of the proteins and RNAs expressed over time during embryogenesis. We present a comprehensive characterization of protein and mRNA dynamics across early development in Xenopus. Surprisingly, we find that most protein levels change little and duplicated genes are expressed similarly. While the correlation between protein and mRNA levels is poor, a mass action kinetics model parameterized using ...[more]

PMID: 26555057

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Project description:INS1-EGFP-L10a stable cell lines were induced with Doxycycline (Dox) for 24 hours, then either untreated or treated for 30 minutes with 1uM Thapsigargin to induce ER stress. Total RNA was purified with Trizol, and RIP RNA samples were extracted by immunoaffinity purification using an EGFP antibody We aimed to determine which genes are enriched under ER stress at the polyribosomal level. To do this we compared expression profiles of Total RNA with and without ER stress, and Immunoaffinity purified RNA (RIP) with and without ER stress. Microarray results of INS-1 EGFP-L10a cells either untreated or treated with 1uM Thapsigargin (Tg) in triplicate. Both Total RNA and RNA isolated from ribosomal Immunoprecipitation (RIP) When unfolded proteins accumulate to irremediably high levels within the endoplasmic reticulum (ER), intracellular signaling pathways called the unfolded protein response (UPR) become hyperactivated to cause programmed cell death. We discovered that thioredoxin-interacting protein (TXNIP) is a critical node in this M-bM-^@M-^\Terminal UPRM-bM-^@M-^]. TXNIP becomes rapidly induced by hyperactivated IRE1a, an ER bifunctional kinase/endoribonuclease (RNase). IRE1a controls TXNIP mRNA stability by reducing levels of a TXNIP destabilizing micro-RNA, miR-17. In turn, elevated TXNIP protein activates the NLRP3 inflammasome, causing Caspase-1 cleavage and interleukin 1b (IL-1b) secretion. Txnip gene deletion reduces pancreatic b-cell death during ER stress, and suppresses diabetes caused by proinsulin misfolding in the Akita mouse. Finally, small molecule IRE1a RNase inhibitors suppress TXNIP production to block IL-1b secretion. In summary, the IRE1a-TXNIP pathway is used in the terminal UPR to promote sterile inflammation and programmed cell death, and may be targeted to develop new treatments for degenerative diseases driven by ER stress. There are 12 samples total all in INS-1 EGFP L10a cells- 3 untreated total RNA (reference sample), 3 treated with 1uM Tg 30 min total RNA, 3 untreated RIP RNA (reference sample), 3 treated with 1uM for 30 min RIP RNA

Dataset Information

On the relationship of protein and mRNA dynamics in vertebrate embryonic development

Publications

On the Relationship of Protein and mRNA Dynamics in Vertebrate Embryonic Development.

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