Transcriptional control of parallel-acting pathways that remove specific presynaptic proteins in remodeling neurons

ABSTRACTSynapses are actively dismantled to mediate circuit refinement, but the developmental pathways that regulate synaptic disassembly are largely unknown. We have previously shown that the epithelial sodium channel UNC-8 triggers an activity-dependent mechanism that drives the removal of presynaptic proteins liprin-α/SYD-2, Synaptobrevin/SNB-1, RAB-3 and Endophilin/UNC-57 in remodeling GABAergic neurons in C. elegans (Miller-Fleming et al., 2016). Here, we report that the transcription factor Iroquois/IRX-1 regulates UNC-8 expression as well as an additional pathway, independent of UNC-8, that functions in parallel to dismantle functional presynaptic terminals. We show that the additional IRX-1-regulated pathway is selectively required for the removal of the presynaptic proteins, Munc13/UNC-13 and ELKS, which normally mediate synaptic vesicle fusion and neurotransmitter release. Our findings are notable because they highlight the key role of transcriptional regulation in synapse elimination and reveal parallel-acting pathways that orchestrate synaptic disassembly by removing specific active zone proteins.

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Nutrient-regulated gene expression in eukaryotes

Biochemical Society Symposium ◽

10.1042/bss0730085 ◽

2006 ◽

Vol 73 ◽

pp. 85-96 ◽

Cited By ~ 8

Author(s):

Richard J. Reece ◽

Laila Beynon ◽

Stacey Holden ◽

Amanda D. Hughes ◽

Karine Rébora ◽

...

Keyword(s):

Gene Expression ◽

Rna Polymerase ◽

Rna Polymerase Ii ◽

Transcriptional Control ◽

Direct Interaction ◽

Signalling Pathways ◽

A Cell ◽

One Step ◽

Higher Eukaryotes ◽

Regulated Gene Expression

The recognition of changes in environmental conditions, and the ability to adapt to these changes, is essential for the viability of cells. There are numerous well characterized systems by which the presence or absence of an individual metabolite may be recognized by a cell. However, the recognition of a metabolite is just one step in a process that often results in changes in the expression of whole sets of genes required to respond to that metabolite. In higher eukaryotes, the signalling pathway between metabolite recognition and transcriptional control can be complex. Recent evidence from the relatively simple eukaryote yeast suggests that complex signalling pathways may be circumvented through the direct interaction between individual metabolites and regulators of RNA polymerase II-mediated transcription. Biochemical and structural analyses are beginning to unravel these elegant genetic control elements.

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P1737 Transcriptional control of telomerase reverse transcriptase in normal endothelial cells. Differences between stimulation by fibroblast growth factor-2 and vascular endothelial growth factor

European Heart Journal ◽

10.1016/s0195-668x(03)94875-5 ◽

2003 ◽

Vol 24 (5) ◽

pp. 331

Author(s):

E TRIVIER

Keyword(s):

Vascular Endothelial Growth Factor ◽

Endothelial Cells ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Transcriptional Control ◽

Fibroblast Growth Factor 2 ◽

Telomerase Reverse Transcriptase ◽

Vascular Endothelial ◽

Fibroblast Growth ◽

Endothelial Growth Factor

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MicroRNAs regulate aldosterone signaling by post-transcriptional control of mineralocorticoid receptor expression

Endocrine Abstracts ◽

10.1530/endoabs.63.p1018 ◽

2019 ◽

Author(s):

Thi-An Vu ◽

Ingrid Lema ◽

Jerome Bouligand ◽

Laetitia Martinerie ◽

Marc Lombes ◽

...

Keyword(s):

Mineralocorticoid Receptor ◽

Transcriptional Control ◽

Receptor Expression

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Post-Transcriptional Regulation of Cardiac Sarcomere Protein Titin Through 3’ Untranslated Regions

Vanderbilt Undergraduate Research Journal ◽

10.15695/vurj.v9i0.3772 ◽

2013 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Tara A Shrout

Keyword(s):

Gene Expression ◽

Transcriptional Control ◽

Striated Muscle ◽

Binding Capacity ◽

Structural Features ◽

Neonatal Rat ◽

Regulatory Control ◽

Untranslated Regions ◽

Luciferase Reporter ◽

Regulatory Effects

Titin is the largest known protein in the human body, and forms the backbone of all striated muscle sarcomeres. The elastic nature of titin is an important component of muscle compliance and functionality. A significant amount of energy is expended to synthesize titin, thus we postulate that titin gene expression is under strict regulatory control in order to conserve cellular resources. In general, gene expression is mediated in part by post-transcriptional control elements located within the 5’ and 3’ untranslated regions (UTRs) of mature mRNA. The 3’UTR in particular contains structural features that affect binding capacity to other RNA components, such as MicroRNA, which control mRNA localization, translation, and degradation. The degree and significance of the regulatory effects mediated by two determined variants of titin’s 3’ UTR were evaluated in Neonatal Rat Ventricular Myocyte and Human Embryonic Kidney cell lines. Recombinant plasmids to transfect these cells lines were engineered by insertion of the variant titin 3’UTR 431- and 1047-base pairs sequences into luciferase reporter vectors. Expression due to an unaltered reporter vector served as the control. Quantitative changes in luciferase activity due to the recombinants proportionally represented the effect titin’s respective 3’UTR conferred on downstream post-transcriptional expression relative to the control. The effect due to titin’s shorter 3’UTR sequence was inconclusive; however, results illustrated that titin’s longer 3’UTR sequence caused a 35 percent decrease in protein expression. Secondary structural analysis of the two sequences revealed differential folding patterns that affect the stability and degree of MicroRNA-binding within titin’s variant 3’UTR sequences.

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