Revealing eEF-2 kinase: recent structural insights into function
We describe recent structural insights into this unique activation process and examine the effects of specific regulatory signals on this mechanism. We also highlight key unanswered questions to guide future structure-function studies. These include structural mechanisms which enable eEF-2K to interact with upstream/downstream partners and facilitate its integration of diverse inputs, including Ca2+ transients, phosphorylation mediated by energy/nutrient-sensing pathways, pH changes, and metabolites. Answering these questions is key to establishing how eEF-2K harmonizes translation with cellular requirements within the bou...
Source: Trends in Biochemical Sciences - December 16, 2023 Category: Biochemistry Authors: Andrea Piserchio Kevin N Dalby Ranajeet Ghose Source Type: research
Revealing eEF-2 kinase: recent structural insights into function
We describe recent structural insights into this unique activation process and examine the effects of specific regulatory signals on this mechanism. We also highlight key unanswered questions to guide future structure-function studies. These include structural mechanisms which enable eEF-2K to interact with upstream/downstream partners and facilitate its integration of diverse inputs, including Ca2+ transients, phosphorylation mediated by energy/nutrient-sensing pathways, pH changes, and metabolites. Answering these questions is key to establishing how eEF-2K harmonizes translation with cellular requirements within the bou...
Source: Trends in Biochemical Sciences - December 16, 2023 Category: Biochemistry Authors: Andrea Piserchio Kevin N Dalby Ranajeet Ghose Source Type: research
Revealing eEF-2 kinase: recent structural insights into function
We describe recent structural insights into this unique activation process and examine the effects of specific regulatory signals on this mechanism. We also highlight key unanswered questions to guide future structure-function studies. These include structural mechanisms which enable eEF-2K to interact with upstream/downstream partners and facilitate its integration of diverse inputs, including Ca2+ transients, phosphorylation mediated by energy/nutrient-sensing pathways, pH changes, and metabolites. Answering these questions is key to establishing how eEF-2K harmonizes translation with cellular requirements within the bou...
Source: Trends in Biochemical Sciences - December 16, 2023 Category: Biochemistry Authors: Andrea Piserchio Kevin N Dalby Ranajeet Ghose Source Type: research
Revealing eEF-2 kinase: recent structural insights into function
We describe recent structural insights into this unique activation process and examine the effects of specific regulatory signals on this mechanism. We also highlight key unanswered questions to guide future structure-function studies. These include structural mechanisms which enable eEF-2K to interact with upstream/downstream partners and facilitate its integration of diverse inputs, including Ca2+ transients, phosphorylation mediated by energy/nutrient-sensing pathways, pH changes, and metabolites. Answering these questions is key to establishing how eEF-2K harmonizes translation with cellular requirements within the bou...
Source: Trends in Biochemical Sciences - December 16, 2023 Category: Biochemistry Authors: Andrea Piserchio Kevin N Dalby Ranajeet Ghose Source Type: research
TRAPs: the 'elevator-with-an-operator' mechanism
Trends Biochem Sci. 2023 Dec 14:S0968-0004(23)00295-5. doi: 10.1016/j.tibs.2023.11.006. Online ahead of print.ABSTRACTTripartite ATP-independent periplasmic (TRAP) transporters are nutrient-uptake systems found in bacteria and archaea. These evolutionary divergent transporter systems couple a substrate-binding protein (SBP) to an elevator-type secondary transporter, which is a first-of-its-kind mechanism of transport. Here, we highlight breakthrough TRAP transporter structures and recent functional data that probe the mechanism of transport. Furthermore, we discuss recent structural and biophysical studies of the ion trans...
Source: Trends in Biochemical Sciences - December 15, 2023 Category: Biochemistry Authors: James S Davies Michael J Currie Renwick C J Dobson Christopher R Horne Rachel A North Source Type: research
TRAPs: the 'elevator-with-an-operator' mechanism
Trends Biochem Sci. 2023 Dec 14:S0968-0004(23)00295-5. doi: 10.1016/j.tibs.2023.11.006. Online ahead of print.ABSTRACTTripartite ATP-independent periplasmic (TRAP) transporters are nutrient-uptake systems found in bacteria and archaea. These evolutionary divergent transporter systems couple a substrate-binding protein (SBP) to an elevator-type secondary transporter, which is a first-of-its-kind mechanism of transport. Here, we highlight breakthrough TRAP transporter structures and recent functional data that probe the mechanism of transport. Furthermore, we discuss recent structural and biophysical studies of the ion trans...
Source: Trends in Biochemical Sciences - December 15, 2023 Category: Biochemistry Authors: James S Davies Michael J Currie Renwick C J Dobson Christopher R Horne Rachel A North Source Type: research
Why U matters: detection and functions of pseudouridine modifications in mRNAs
Trends Biochem Sci. 2023 Dec 14:S0968-0004(23)00277-3. doi: 10.1016/j.tibs.2023.10.008. Online ahead of print.ABSTRACTThe uridine modifications pseudouridine (Ψ), dihydrouridine, and 5-methyluridine are present in eukaryotic mRNAs. Many uridine-modifying enzymes are associated with human disease, underscoring the importance of uncovering the functions of uridine modifications in mRNAs. These modified uridines have chemical properties distinct from those of canonical uridines, which impact RNA structure and RNA-protein interactions. Ψ, the most abundant of these uridine modifications, is present across (pre-)mRNAs. Recent...
Source: Trends in Biochemical Sciences - December 14, 2023 Category: Biochemistry Authors: Rebecca Rodell Nicolas Robalin Nicole M Martinez Source Type: research
Why U matters: detection and functions of pseudouridine modifications in mRNAs
Trends Biochem Sci. 2023 Dec 14:S0968-0004(23)00277-3. doi: 10.1016/j.tibs.2023.10.008. Online ahead of print.ABSTRACTThe uridine modifications pseudouridine (Ψ), dihydrouridine, and 5-methyluridine are present in eukaryotic mRNAs. Many uridine-modifying enzymes are associated with human disease, underscoring the importance of uncovering the functions of uridine modifications in mRNAs. These modified uridines have chemical properties distinct from those of canonical uridines, which impact RNA structure and RNA-protein interactions. Ψ, the most abundant of these uridine modifications, is present across (pre-)mRNAs. Recent...
Source: Trends in Biochemical Sciences - December 14, 2023 Category: Biochemistry Authors: Rebecca Rodell Nicolas Robalin Nicole M Martinez Source Type: research
Molecular mechanisms of the RNA polymerases in plant RNA-directed DNA methylation
Trends Biochem Sci. 2023 Dec 9:S0968-0004(23)00294-3. doi: 10.1016/j.tibs.2023.11.005. Online ahead of print.ABSTRACTIn plants, two atypical DNA-dependent RNA polymerases, RNA polymerase IV (Pol IV) and Pol V, and an RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) together produce noncoding RNAs (ncRNAs) to guide the plant-specific RNA-directed DNA methylation (RdDM). Although both Pol IV and Pol V have evolved from the canonical Pol II, they have adapted to different roles in RdDM. The mechanisms of their adaptation are key to understanding plant DNA methylation and the divergent evolution of polymerases. In this review, we summari...
Source: Trends in Biochemical Sciences - December 10, 2023 Category: Biochemistry Authors: Guohui Xie Xuan Du Hongmiao Hu Jiamu Du Source Type: research
Molecular mechanisms of the RNA polymerases in plant RNA-directed DNA methylation
Trends Biochem Sci. 2023 Dec 9:S0968-0004(23)00294-3. doi: 10.1016/j.tibs.2023.11.005. Online ahead of print.ABSTRACTIn plants, two atypical DNA-dependent RNA polymerases, RNA polymerase IV (Pol IV) and Pol V, and an RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) together produce noncoding RNAs (ncRNAs) to guide the plant-specific RNA-directed DNA methylation (RdDM). Although both Pol IV and Pol V have evolved from the canonical Pol II, they have adapted to different roles in RdDM. The mechanisms of their adaptation are key to understanding plant DNA methylation and the divergent evolution of polymerases. In this review, we summari...
Source: Trends in Biochemical Sciences - December 10, 2023 Category: Biochemistry Authors: Guohui Xie Xuan Du Hongmiao Hu Jiamu Du Source Type: research
Molecular mechanisms of the RNA polymerases in plant RNA-directed DNA methylation
Trends Biochem Sci. 2023 Dec 9:S0968-0004(23)00294-3. doi: 10.1016/j.tibs.2023.11.005. Online ahead of print.ABSTRACTIn plants, two atypical DNA-dependent RNA polymerases, RNA polymerase IV (Pol IV) and Pol V, and an RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) together produce noncoding RNAs (ncRNAs) to guide the plant-specific RNA-directed DNA methylation (RdDM). Although both Pol IV and Pol V have evolved from the canonical Pol II, they have adapted to different roles in RdDM. The mechanisms of their adaptation are key to understanding plant DNA methylation and the divergent evolution of polymerases. In this review, we summari...
Source: Trends in Biochemical Sciences - December 10, 2023 Category: Biochemistry Authors: Guohui Xie Xuan Du Hongmiao Hu Jiamu Du Source Type: research
Molecular mechanisms of the RNA polymerases in plant RNA-directed DNA methylation
Trends Biochem Sci. 2023 Dec 9:S0968-0004(23)00294-3. doi: 10.1016/j.tibs.2023.11.005. Online ahead of print.ABSTRACTIn plants, two atypical DNA-dependent RNA polymerases, RNA polymerase IV (Pol IV) and Pol V, and an RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) together produce noncoding RNAs (ncRNAs) to guide the plant-specific RNA-directed DNA methylation (RdDM). Although both Pol IV and Pol V have evolved from the canonical Pol II, they have adapted to different roles in RdDM. The mechanisms of their adaptation are key to understanding plant DNA methylation and the divergent evolution of polymerases. In this review, we summari...
Source: Trends in Biochemical Sciences - December 10, 2023 Category: Biochemistry Authors: Guohui Xie Xuan Du Hongmiao Hu Jiamu Du Source Type: research
mRNA accessibility within mRNPs as a determinant of gene expression
Trends Biochem Sci. 2023 Dec 8:S0968-0004(23)00287-6. doi: 10.1016/j.tibs.2023.11.003. Online ahead of print.ABSTRACTGene expression is a complex process requiring many control mechanisms to achieve a desired phenotype. DNA accessibility within chromatin is well established as an important determinant of gene expression. By contrast, while mRNA also associates with a complement of proteins, the exact nature of messenger ribonucleoprotein (mRNP) packaging and its functional relevance is not as clear. Recent reports indicate that exon junction complex (EJC)-mediated mRNP packaging renders exon junction-proximal regions inacc...
Source: Trends in Biochemical Sciences - December 9, 2023 Category: Biochemistry Authors: P Cody He Chuan He Source Type: research
Causes and consequences of DNA single-strand breaks
Trends Biochem Sci. 2023 Nov 30:S0968-0004(23)00285-2. doi: 10.1016/j.tibs.2023.11.001. Online ahead of print.ABSTRACTDNA single-strand breaks (SSBs) are among the most common lesions arising in human cells, with tens to hundreds of thousands arising in each cell, each day. Cells have efficient mechanisms for the sensing and repair of these ubiquitous DNA lesions, but the failure of these processes to rapidly remove SSBs can lead to a variety of pathogenic outcomes. The threat posed by unrepaired SSBs is illustrated by the existence of at least six genetic diseases in which SSB repair (SSBR) is defective, all of which are ...
Source: Trends in Biochemical Sciences - December 1, 2023 Category: Biochemistry Authors: Keith W Caldecott Source Type: research
Causes and consequences of DNA single-strand breaks
Trends Biochem Sci. 2023 Nov 30:S0968-0004(23)00285-2. doi: 10.1016/j.tibs.2023.11.001. Online ahead of print.ABSTRACTDNA single-strand breaks (SSBs) are among the most common lesions arising in human cells, with tens to hundreds of thousands arising in each cell, each day. Cells have efficient mechanisms for the sensing and repair of these ubiquitous DNA lesions, but the failure of these processes to rapidly remove SSBs can lead to a variety of pathogenic outcomes. The threat posed by unrepaired SSBs is illustrated by the existence of at least six genetic diseases in which SSB repair (SSBR) is defective, all of which are ...
Source: Trends in Biochemical Sciences - December 1, 2023 Category: Biochemistry Authors: Keith W Caldecott Source Type: research
