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Biology subjects

Jennings, M. D.

Publications and source records attributed to Jennings, M. D..

2 recordsLinked to original sources

Integrated multi-omics reveals common properties underlying stress granule and P-body formation

Non-membrane-bound compartments such as P-bodies (PBs) and stress granules (SGs) play important roles in the regulation of gene expression following environmental stresses. We have systematically determined the protein and mRNA composition of PBs and SGs formed in response to a common stress condition imposed by glucose depletion. We find that high molecular weight (HMW) complexes exist prior to glucose depletion that may act as seeds for the further condensation of proteins forming mature PBs and SGs. Both before and after glucose depletion, these HMW complexes are enriched for proteins containing low complexity and RNA binding domains. The mRNA content of these HMW complexes is enriched for long, structured mRNAs that become more poorly translated following glucose depletion. Many proteins and mRNAs are shared between PBs and SGs including several multivalent RNA binding proteins that may promote condensate interactions during liquid-liquid phase separation. Even where the precise identity of mRNAs and proteins localizing to PBs and SGs is distinct, the mRNAs and proteins share common biophysical and chemical features that likely trigger their phase separation.

biochemistry↗

The structural basis of translational control by eIF2 phosphorylation

Protein synthesis in eukaryotes is controlled by signals and stresses via a common pathway, called the integrated stress response (ISR). Phosphorylation of the translation initiation factor eIF2 alpha at a conserved serine residue mediates translational control at the ISR core. To provide insight into the mechanism of translational control we have determined the structures of eIF2 both in phosphorylated and unphosphorylated forms bound with its nucleotide exchange factor eIF2B by cryo-electron microscopy. The structures reveal that eIF2 undergoes large rearrangements to promote binding of eIF2 to the regulatory core of eIF2B comprised of the eIF2B alpha, beta and delta subunits. Only minor differences are observed between eIF2 and eIF2P binding to eIF2B suggesting that the higher affinity of eIF2P for eIF2B drives translational control. We present a model for controlled nucleotide exchange and initiator tRNA binding to the eIF2/eIF2B complex.

molecular biology↗