mTOR referees memory and disease through mRNA repression and competition

Abstract

Mammalian target of rapamycin (mTOR) activity is required for memory and is dysregulated in disease. Activation of mTOR promotes protein synthesis; however, new studies are demonstrating that mTOR activity also represses the translation of mRNAs. Almost three decades ago, Kandel and colleagues hypothesised that memory was due to the induction of positive regulators and removal of negative constraints. Are these negative constraints repressed mRNAs that code for proteins that block memory formation? Herein, we will discuss the mRNAs coded by putative memory suppressors, how activation/inactivation of mTOR repress protein expression at the synapse, how mTOR activity regulates RNA binding proteins, mRNA stability, and translation, and what the possible implications of mRNA repression are to memory and neurodegenerative disorders.

Differential profile of protein expression on human keratocytes treated with autologous serum and plasma rich in growth factors (PRGF)

“…Several studies have demonstrated that an alteration in EIF2 pathway is related to the development of neurodegenerative, metabolic and cancer diseases [ 37 , 38 ], while EIF4 is a protein complex involved in mRNA translation implicated in cell proliferation [ 39 ]. In addition, mTOR is involved in the control of mRNA transcription, ribosome formation, cell cytoskeleton organization, cell membrane transport, regulation of cell growth, proliferation and death [ 40 – 42 ]. Our results provide a link between PRGF-Endoret function and protein synthesis, cell proliferation and motility, since these results are more significantly related to this condition.…”

AMPA Receptors: A Key Piece in the Puzzle of Memory Retrieval

“…Among the potential upstream modulators of AMPAR movements at the synapse, mTORC1 has been proposed to play a pivotal role in memory processes ( Bekinschtein et al, 2007 ; Lopez et al, 2015 ; Pereyra et al, 2021 ). mTORC1 regulates local protein translation in dendrites ( Tang et al, 2002 ; Hay and Sonenberg, 2004 ; Hoeffer and Klann, 2010 ; Raab-Graham and Niere, 2017 ) and its blockade is associated with downregulation of GluA1 levels during memory retrieval in the PSD ( Lopez et al, 2015 ; Pereyra et al, 2021 ) ( Figure 1B ). In the hippocampus, but not in the amygdala, downregulation of GluA1 levels is also observed in the synaptic plasma membrane fraction in rapamycin (selective mTORC1 inhibitor)-treated animals ( Lopez et al, 2015 ; Pereyra et al, 2021 ).…”

Mirroring the multifaceted role of RNA and its partners in gene expression

“…Therefore, the discovery of new types of RNA molecules went hand in hand with the unearthing of new RNA‐binding proteins that specifically or promiscuously interact with RNAs to implement various functions. In this respect, FEBS Letters published recently a series of review articles related to RNA‐binding proteins and their cellular and neuronal functions (https://febs.onlinelibrary.wiley.com/doi/toc/10.1002/(ISSN)1873-3468.MRNATRANSPORT) . The present Special Issue extends this series by highlighting recent topics in RNA research such as RNA modifications, RNA‐RNA and RNA‐protein interactions, and RNA‐regulated pathways.…”

“…. mRNA transport, local translation and processing) [12][13][14][15][16][17]. The present Special Issue extends this series by highlighting recent topics in RNA research such as RNA modifications, RNA-RNA and RNA-protein interactions, and RNAregulated pathways.…”