Ribonuclease inhibitor (RNH1) is a ribosome-associated protein and regulates erythropoiesis by controlling GATA1-specific mRNA translation

Allam, Ramanjaneyulu; Chennupati, Vijaykumar; Veiga, Diogo F.T.; Maslowski, Kendle M.; Tardivel, Aubry; Andina, Nicola; Yu, Eric Chi-Wang; Stilinovic, Martina; Simillion, Cédric; Duchosal, Michel A.; Quadroni, Manfredo; Roberts, Irene; Sankaran, Vijay G.; MacDonald, H. Robson; Angelillo‐Scherrer, Anne; Schneider, Pascal; Hoang, Trang

doi:10.1016/j.exphem.2017.06.338

Cited by 3 publications

(7 citation statements)

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“…It is not surprising, therefore, that exogenous treatment using various ribonucleases can degrade monoribosomes into “dust‐like” fragments in vitro (Steward, ; Rubel et al, ) [see also (Blasi et al, ; Gerashchenko and Gladyshev, )]. Interestingly, endogenous ribonucleases accompany ribosomes (Bransgrove and Cosquer, ; Bates et al, ; Bates et al, ; Schoenberg and Maquat, ) including in the adult mammalian brain (Datta and Ghosh, ) presumably constrained by an endogenous inhibitor (Allam et al, ). As will be seen next, particular ribonucleases are plausibly responsible for fragmentation of rough endoplasmic reticulum, dissociation of polyribosomes, degradation of monoribosomes and decay of RNA (Table ).…”

Section: Do Ribonucleases Cause Fragmentation Dispersal and Degranulmentioning

confidence: 99%

“…There is one report that chromatolysis can be prevented by protein synthesis inhibitors (Torvik and Heding, ) indicating that chromatolysis may be due to a newly‐synthesized enzyme (Bates et al, ; Mami et al, ). Alternatively, perhaps ribonucleases that are associated with ribosomes (Datta and Ghosh, ; Bransgrove and Cosquer, ; Bates et al, ; Bates et al, ; Schoenberg and Maquat, ) become activated after injury (Allam et al, ). Ribonucleases are also known to change their subcellular distribution after injury or during stress (Ivanov and Anderson, ; Nicholson, ).…”

Section: Which Ribonuclease(s) Might Cause Fragmentation Of Rough Endmentioning

confidence: 99%

“…The secreted vertebrate family of ribonucleases is normally tightly controlled by the mammalian Ribonuclease Inhibitor 1 (RNH1) (Dickson et al, ). RNH1 is found primarily in the cytoplasm, where it binds to these RNases with remarkably high affinities (Dickson et al, ) and inhibits their activities, although it can also be found in the nucleus, in mitochondria, in stress granules (Furia et al, ) and associated with ribosomes (Allam et al, ). Cytoplasmic inhibition of ribonucleases is disrupted in cellular stress situations, e.g., by oxidative stress (Dickson et al, ): net activity of ribonucleases is increased transiently in SCG during chromatolysis (Bates et al, ).…”

Section: Why Don't Endogenous Potent Ribonucleases Constitutively Camentioning

confidence: 99%

“…Unfettered ribonucleases might then degrade polyribosomes (into free monoribosomes) and monoribosomes (into ribosome fragments). Indeed, RNH1 deficiency leads to decreased polyribosome formation whereas overexpression of RNH1 promotes polyribosome formation (Allam et al, ). During stress in non‐neuronal cells, RNH1 is translocated to the nucleus and Ribonuclease 5 is exported from the nucleus (Pizzo et al, ).…”

Section: Why Don't Endogenous Potent Ribonucleases Constitutively Camentioning

confidence: 99%

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Chromatolysis: Do injured axons regenerate poorly when ribonucleases attack rough endoplasmic reticulum, ribosomes and RNA?

Moon

2018

Developmental Neurobiology

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After axonal injury, chromatolysis (fragmentation of Nissl substance) can occur in the soma. Electron microscopy shows that chromatolysis involves fission of the rough endoplasmic reticulum. In CNS neurons (which do not regenerate axons back to their original targets) or in motor neurons or dorsal root ganglion neurons denied axon regeneration (e.g., by transection and ligation), chromatolysis is often accompanied by degranulation (loss of ribosomes from rough endoplasmic reticulum), disaggregation of polyribosomes and degradation of monoribosomes into dust-like particles. Ribosomes and rough endoplasmic reticulum may also be degraded in autophagic vacuoles by ribophagy and reticulophagy, respectively. In other words, chromatolysis is disruption of parts of the protein synthesis infrastructure. Whereas some neurons may show transient or no chromatolysis, severely injured neurons can remain chromatolytic and never again synthesize normal levels of protein; some may atrophy or die. Ribonuclease(s) might cause the following features of chromatolysis: fragmentation and degranulation of rough endoplasmic reticulum, disaggregation of polyribosomes and degradation of monoribosomes. For example, ribonucleases in the EndoU/PP11 family can modify rough endoplasmic reticulum; many ribonucleases can degrade mRNA causing polyribosomes to unchain and disperse, and they can disassemble monoribosomes; Ribonuclease 5 can control rRNA synthesis and degrade tRNA; Ribonuclease T2 can degrade ribosomes, endoplasmic reticulum and RNA within autophagic vacuoles; and Ribonuclease IRE1α acts as a stress sensor within the endoplasmic reticulum. Regeneration might be improved after axonal injury by protecting the protein synthesis machinery from catabolism; targeting ribonucleases using inhibitors can enhance neurite outgrowth and could be a profitable strategy in vivo. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018.

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Section: Do Ribonucleases Cause Fragmentation Dispersal and Degranulmentioning

confidence: 99%

Section: Which Ribonuclease(s) Might Cause Fragmentation Of Rough Endmentioning

confidence: 99%

Section: Why Don't Endogenous Potent Ribonucleases Constitutively Camentioning

confidence: 99%

Section: Why Don't Endogenous Potent Ribonucleases Constitutively Camentioning

confidence: 99%

See 2 more Smart Citations

Chromatolysis: Do injured axons regenerate poorly when ribonucleases attack rough endoplasmic reticulum, ribosomes and RNA?

Moon

2018

Developmental Neurobiology

View full text Add to dashboard Cite

show abstract

“…It is not surprising, therefore, that exogenous treatment using various ribonucleases can degrade monoribosomes into "dustlike" fragments in vitro (Steward, 1983;Rubel et al, 1991) [see also (Blasi et al, 2000;Gerashchenko and Gladyshev, 2017)]. Interestingly, endogenous ribonucleases accompany ribosomes (Bransgrove and Cosquer, 1978;Bates et al, 1985a;Bates et al, 1987;Schoenberg and Maquat, 2012) including in the adult mammalian brain (Datta and Ghosh, 1962) presumably constrained by an endogenous inhibitor (Allam et al, 2017) (see below). As will be seen next, particular ribonucleases are plausibly responsible for fragmentation of rough endoplasmic reticulum, dissociation of polyribosomes, degradation of monoribosomes and decay of RNA.…”

Section: Do Ribonucleases Cause Fragmentation Dispersal and Degranulmentioning

confidence: 99%

Chromatolysis: Do Injured Axons Regenerate Poorly when Ribonucleases Fragment or Degranulate Rough Endoplasmic Reticulum, Disaggregate Polyribosomes, Degrade Monoribosomes and Lyse RNA?

Moon¹

2018

Preprint

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After axonal injury, chromatolysis (fragmentation of Nissl substance) occurs in both intrinsic neurons (whose processes are within the CNS) and extrinsic neurons (whose axons extend outside the CNS). Electron microscopy shows that chromatolysis involves fission of the rough endoplasmic reticulum. In intrinsic neurons (which do not regenerate axons) or in extrinsic neurons denied axon regeneration, chromatolysis is often accompanied by degranulation (loss of ribosomes from rough endoplasmic reticulum), disaggregation of polyribosomes and degradation of monoribosomes into dust-like particles. Ribosomes and rough endoplasmic reticulum may also be degraded in autophagic vacuoles by Ribophagy and Reticulophagy, respectively. In other words, chromatolysis is disruption of parts of the protein synthesis infrastructure. Whereas some neurons may show transient or no chromatolysis, severely injured neurons can remain chromatolytic and never again synthesise normal levels of protein; some may atrophy or die. What molecule(s) cause fragmentation or degranulation of rough endoplasmic reticulum, disaggregation of polyribosomes and degradation of monoribosomes? Ribonucleases can modify (and perhaps fragment) rough endoplasmic reticulum; various endoribonucleases can degrade mRNA causing polyribosomes to unchain and disperse; they can disassemble monoribosomes; Ribonuclease 5 can control rRNA synthesis and degrade tRNA; Ribonuclease T2 can degrade ribosomes, rough endoplasmic reticulum and RNA within autophagic vacuoles; and Ribonuclease IRE1α acts as a stress sensor within the endoplasmic reticulum. Regeneration might be improved after axonal injury by protecting the protein synthesis machinery from catabolism; targeting ribonucleases could be a profitable strategy.

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Functional status analysis of RNH1 in bladder cancer for predicting immunotherapy response

Chen

Ran

Fan

et al. 2023

Sci Rep

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Bladder cancer (BLCA) typically has a poor prognosis due to high rates of relapse and metastasis. Although the emergence of immunotherapy brings hope for patients with BLCA, not all patients will benefit from it. Identifying some markers to predict treatment response is particularly important. Here, we aimed to determine the clinical value of the ribonuclease/angiogenin inhibitor 1 (RNH1) in BLCA therapy based on functional status analysis. First, we found that RNH1 is aberrantly expressed in multiple cancers but is associated with prognosis in only a few types of cancer. Next, we determined that low RNH1 expression was significantly associated with enhanced invasion and metastasis of BLCA by assessing the relationship between RNH1 and 17 functional states. Moreover, we identified 95 hub genes associated with invasion and metastasis among RNH1-related genes. Enrichment analysis revealed that these hub genes were also significantly linked with immune activation. Consistently, BLCA can be divided into two molecular subtypes based on these hub genes, and the differentially expressed genes between the two subtypes are also significantly enriched in immune-related pathways. This indicates that the expression of RNH1 is also related to the tumour immune response. Subsequently, we confirmed that RNH1 shapes an inflammatory tumour microenvironment (TME), promotes activation of the immune response cycle steps, and has the potential to predict the immune checkpoint blockade (ICB) treatment response. Finally, we demonstrated that high RNH1 expression was significantly associated with multiple therapeutic signalling pathways and drug targets in BLCA. In conclusion, our study revealed that RNH1 could provide new insights into the invasion of BLCA and predict the immunotherapy response in patients with BLCA.

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Ribonuclease inhibitor (RNH1) is a ribosome-associated protein and regulates erythropoiesis by controlling GATA1-specific mRNA translation

Cited by 3 publications

References 0 publications

Chromatolysis: Do injured axons regenerate poorly when ribonucleases attack rough endoplasmic reticulum, ribosomes and RNA?

Chromatolysis: Do injured axons regenerate poorly when ribonucleases attack rough endoplasmic reticulum, ribosomes and RNA?

Chromatolysis: Do Injured Axons Regenerate Poorly when Ribonucleases Fragment or Degranulate Rough Endoplasmic Reticulum, Disaggregate Polyribosomes, Degrade Monoribosomes and Lyse RNA?

Functional status analysis of RNH1 in bladder cancer for predicting immunotherapy response

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