About this Research Topic
Maintaining proteome integrity is an essential prerequisite for normal cellular functions. Nascent proteins (NP) are quality assured by various mechanisms before being released into the cytosol or transported to specific organelles. One of the key mechanisms that monitor aberrant proteins involves the ribosomes themselves, in a process termed ribosome
associated quality control (RQC). The RQC monitors the aberrant stalling, translation arrest, and ribosomal collision during the process of translation. Under translational stress conditions, the ribosomes collide with each other to form disomes (two ribosomes collided) or trisomes (three ribosomes collided). These collided ribosomes are specifically recognized by ubiquitin ligase, ZNF598. ZNF598 docks onto these collided ribosomes and ubiquitinates ribosomal proteins like RPS3, RPS10, and RPS20. These ubiquitinated proteins serve as a signal for the recruitment of other RQC proteins like ABCE1, NEMF, and VCP. Once associated with the stalled ribosomes, these proteins separate the 40S subunit from the 60S ribosomal subunit anchored with a nascent polypeptide chain (NPC). The 40S subunit is recycled while the released mRNA is degraded via one of the three different mechanisms called as nonsense mediated decay (NMD), No Go Decay (NGD) and Non Stop Decay (NSD). On the other hand, NPC anchored 60S subunit is rescued by mRNA template independent addition of Alanine and Threonine residues by NEMF on the C-Terminus of NPC thus termed as CAT tailing. CAT tailing ensures the effective removal of the trapped NPC via the VCP protein complex associated with RQC proteins. Listerin 1 then ubiquitinates these CAT tailed NPC and thus helps in their degradation via the proteasome.
The collective effort of some fascinating group of proteins resolves stalled translation, rescues trapped 60S and 40S ribosomal subunits and degrades the truncated polypeptide chain. The functional significance of this process is now emerging and it seems to play a critical role in neurodegeneration and cancer. Also, the individual proteins involved in this process like NEMF, ZNF598, and VCP have been shown to play roles in mitochondrial health and metabolism.
In this Research Topic, we will focus on the recent developments in the RQC both at process level as well as on the role of individual proteins involved in this process. We are accepting review articles on a range of topics covering RQC of both stalled NPC and truncated/abnormal mRNAs. We will be focussing on the emerging roles of ribosomal quality control at a process level as well as we will explore the roles of RQC core machinery proteins in neurodegeneration and cancer.
Following are the main areas of interest in this Research Topic:
- Structure and mechanism of ribosomal quality control machinery.
- Signaling pathways of ribosomal quality control proteins.
- Structural modification in ribosomal quality control proteins during pathological and physiological conditions.
- Role of ribosomal quality control proteins in disease progression.
- Screening of ribosomal quality control proteins as a biomarker in disease progression
- Identification or developments of molecular targets related to ribosomal quality control proteins in the treatment of cancer and neurodegeneration.
- Role of mRNA quality control in neurodegeneration and cancer.
- Mechanism of mRNA quality control pathways in mammals.
associated quality control (RQC). The RQC monitors the aberrant stalling, translation arrest, and ribosomal collision during the process of translation. Under translational stress conditions, the ribosomes collide with each other to form disomes (two ribosomes collided) or trisomes (three ribosomes collided). These collided ribosomes are specifically recognized by ubiquitin ligase, ZNF598. ZNF598 docks onto these collided ribosomes and ubiquitinates ribosomal proteins like RPS3, RPS10, and RPS20. These ubiquitinated proteins serve as a signal for the recruitment of other RQC proteins like ABCE1, NEMF, and VCP. Once associated with the stalled ribosomes, these proteins separate the 40S subunit from the 60S ribosomal subunit anchored with a nascent polypeptide chain (NPC). The 40S subunit is recycled while the released mRNA is degraded via one of the three different mechanisms called as nonsense mediated decay (NMD), No Go Decay (NGD) and Non Stop Decay (NSD). On the other hand, NPC anchored 60S subunit is rescued by mRNA template independent addition of Alanine and Threonine residues by NEMF on the C-Terminus of NPC thus termed as CAT tailing. CAT tailing ensures the effective removal of the trapped NPC via the VCP protein complex associated with RQC proteins. Listerin 1 then ubiquitinates these CAT tailed NPC and thus helps in their degradation via the proteasome.
The collective effort of some fascinating group of proteins resolves stalled translation, rescues trapped 60S and 40S ribosomal subunits and degrades the truncated polypeptide chain. The functional significance of this process is now emerging and it seems to play a critical role in neurodegeneration and cancer. Also, the individual proteins involved in this process like NEMF, ZNF598, and VCP have been shown to play roles in mitochondrial health and metabolism.
In this Research Topic, we will focus on the recent developments in the RQC both at process level as well as on the role of individual proteins involved in this process. We are accepting review articles on a range of topics covering RQC of both stalled NPC and truncated/abnormal mRNAs. We will be focussing on the emerging roles of ribosomal quality control at a process level as well as we will explore the roles of RQC core machinery proteins in neurodegeneration and cancer.
Following are the main areas of interest in this Research Topic:
- Structure and mechanism of ribosomal quality control machinery.
- Signaling pathways of ribosomal quality control proteins.
- Structural modification in ribosomal quality control proteins during pathological and physiological conditions.
- Role of ribosomal quality control proteins in disease progression.
- Screening of ribosomal quality control proteins as a biomarker in disease progression
- Identification or developments of molecular targets related to ribosomal quality control proteins in the treatment of cancer and neurodegeneration.
- Role of mRNA quality control in neurodegeneration and cancer.
- Mechanism of mRNA quality control pathways in mammals.
Keywords: Ribosomal Quality Control (RQC), Neurodegeneration, Cancer, Ubiquitination
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