ELAC1 Repairs tRNAs Cleaved during Ribosome-Associated Quality Control

Yip, M.C.J.; Savickas, Simonas; Gygi, Steven P.; Shao, Sichen

doi:10.1016/j.celrep.2020.01.082

Cited by 31 publications

(22 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ELAC2 has been shown to colocalize with nuclei and mitochondria, whereas ELAC1 resides in the cytosol ( Takahashi et al, 2008 ). Until recently, only little was known about ELAC1 function but a new study has shown that ELAC1 has a role in tRNA recycling, which takes place in cytosol and, thus, cannot be completed by ELAC2 ( Yip et al, 2020 ). It appears that in flies, RNAseZ carries out functions that are in humans performed by both ELAC1 and ELAC2.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, humans have two forms of this protein: long ELAC2 (RNaseZ L ), and short ELAC1 (RNaseZ S ), while (Takahashi et al, 2008). Little was known about ELAC1 activity until recent study has showed that it has a role in tRNA recycling, which takes place in cytosol, and thus, cannot be completed by ELAC2 (Yip et al, 2020). It appears that in flies, dRNAseZ carries out functions performed by both ELAC1 and ELAC2 in humans.…”

Section: Partial Functional Homology Of Elac2 and Drnasezmentioning

confidence: 99%

See 1 more Smart Citation

ELAC2/RNaseZ-linked cardiac hypertrophy in Drosophila melanogaster

Мигунова

Theophilopoulos

Mercadante

et al. 2021

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

A severe form of infantile cardiomyopathy (CM) has been linked to ELAC2 gene mutations. ELAC2 is a highly conserved human gene. It encodes RNaseZL endoribonuclease that plays an essential role in the production of mature tRNAs. To establish a causal connection between ELAC2 variants and CM, here we use a model organism Drosophila melanogaster, which carries ELAC2 homolog - dRNaseZ. Even though dRNaseZ and ELAC2 have diverged in some of their biological functions, our study demonstrates the utility of the fly model to study the mechanism of ELAC2 related pathology. We established transgenic lines harboring dRNaseZ with CM-linked mutations in the background of endogenous dRNaseZ knockout. Importantly, we found that the phenotype of these flies is consistent with pathological features in human patients. Specifically, expression of CM-linked variants in flies causes heart hypertrophy and leads to reduction in cardiac contractility associated with a rare form of CM. This study provides first experimental evidence for the pathogenicity of CM-causing mutations in the ELAC2 protein and lay the foundation to improve our understanding and diagnosis of this rare infantile disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Partial Functional Homology Of Elac2 and Drnasezmentioning

confidence: 99%

ELAC2/RNaseZ-linked cardiac hypertrophy in Drosophila melanogaster

Мигунова

Theophilopoulos

Mercadante

et al. 2021

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…The relative affinity of tRNA for exportin-t/RangGTP is 10 times lower when tRNA is without 3-CCA, and 6 times weaker when tRNA carries only 3-CC (Lipowsky et al 1999). Therefore, ALKBH8 might bind to tRNAs lacking 3-CCA due to the activity of ANKZF1 and ELAC1 (Yip et al 2019, 2020). The incomplete CCA termini are repaired by a cytosolic population of CCA-transferase (Wolfe et al 1996).…”

Section: Resultsmentioning

confidence: 99%

HITS-CLIP analysis of human ALKBH8 points towards its role in tRNA and noncoding RNA regulation

Cavallin

Bartošovič

Skalický

et al. 2022

Preprint

View full text Add to dashboard Cite

Transfer RNAs acquire a large plethora of chemical modifications. Among those, modifications of the anticodon loop play important roles in translational fidelity and tRNA stability. Four human wobble U containing tRNAs obtain 5-methoxycarbonylmethyluridine (mcm5U34) or 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U34), which play a role in decoding. This mark involves a cascade of enzymatic activities. The last step is mediated by Alkylation Repair Homolog 8 (ALKBH8). In this study, we performed a transcriptome-wide analysis of the repertoire of ALKBH8 RNA targets. Using a combination of HITS-CLIP-seq and RIP-seq analyses, we uncover ALKBH8-bound RNAs. It targets an additional wobble U-containing tRNA tRNALys(UUU). More interestingly, the spectrum of bound RNAs includes other types of non-coding RNAs, such as C/D box snoRNAs, 7SK RNA or some miRNAs, respectively.

show abstract

“…In this process stalled ribosomes induce the recruitment of ANKZF1 that releases the nascent peptides from the peptidyl-tRNA by cleaving the CCA-tail ( 49 ). While the nascent peptide is tagged for proteasome degradation the shortened tRNA is repaired by TRNT1 (the human CAE) after the cyclic phosphate is removed by ELAC1 ( 50 ). In contrast to the E. coli enzyme the trypanosome CAE does not contain an HD domain and should therefore be unable to resolve any 2′,3′-cyclic phosphate left behind by the nuclease that trims the tRNAs ( 51 ).…”

Section: Discussionmentioning

confidence: 99%

tRNA 3′ shortening by LCCR4 as a response to stress in Trypanosoma brucei

Cristodero

Brogli

Joss

et al. 2021

Nucleic Acids Research

View full text Add to dashboard Cite

Sensing of environmental cues is crucial for cell survival. To adapt to changes in their surroundings cells need to tightly control the repertoire of genes expressed at any time. Regulation of translation is key, especially in organisms in which transcription is hardly controlled, like Trypanosoma brucei. In this study, we describe the shortening of the bulk of the cellular tRNAs during stress at the expense of the conserved 3′ CCA-tail. This tRNA shortening is specific for nutritional stress and renders tRNAs unsuitable substrates for translation. We uncovered the nuclease LCCR4 (Tb927.4.2430), a homologue of the conserved deadenylase Ccr4, as being responsible for tRNA trimming. Once optimal growth conditions are restored tRNAs are rapidly repaired by the trypanosome tRNA nucleotidyltransferase thus rendering the recycled tRNAs amenable for translation. This mechanism represents a fast and efficient way to repress translation during stress, allowing quick reactivation with a low energy input.

show abstract

ELAC1 Repairs tRNAs Cleaved during Ribosome-Associated Quality Control

Cited by 31 publications

References 58 publications

ELAC2/RNaseZ-linked cardiac hypertrophy in Drosophila melanogaster

ELAC2/RNaseZ-linked cardiac hypertrophy in Drosophila melanogaster

HITS-CLIP analysis of human ALKBH8 points towards its role in tRNA and noncoding RNA regulation

tRNA 3′ shortening by LCCR4 as a response to stress in Trypanosoma brucei

Contact Info

Product

Resources

About