Biology subjects

Fu, G.

Publications and source records attributed to Fu, G..

At least 19 recordsLinked to original sources

bioRxiv2025

Multi-Dimensional Spatiotemporal Attention Neural Network for Next Generation Sequencing Basecalling

Next-generation sequencing (NGS) remains the most used sequencing technique in the field of genomics. Traditional basecall methods face significant challenges in decoding high density sequencing data due to inherent noise in biochemical reactions and limitations of instruments. Here, we present a multi-dimensional deep learning neural network based on spatiotemporal attention mechanism named AICall. The network skips computationally heavy but less effective steps of peak finding and brightness extraction/correction, and directly basecalls from the time sequence of multi-dimensional image stacks obtained in real time. By introducing attention mechanism, it effectively extracts spatial and time-related key information including spatial crosstalk, spectral crosstalk, phasing, base-quenching, and intensity decay, and significantly improves basecall accuracy. We demonstrate that AICall achieves an average error rate less than 0.01% and provides more reliable sequencing results for downstream analysis.

bioinformatics↗

bioRxiv2025

APOE knockout attenuates vascular graft fibrosis by limiting profibrotic macrophage formation through low-density lipoprotein receptor related protein 1

Vascular graft fibrosis can cause a decrease in cellular infiltration and capillary ingrowth in vascular walls and vascular stiffening. As such, there are still no vascular grafts that can be used in blood vessels where their diameters are less than 6 mm in patients. Although various approaches have been evaluated to mitigate implant-associated fibrosis, effective treatments remain quite limited. In this study, we demonstrated that APOE was significantly increased during vascular regeneration after graft implantation in vivo. APOE knockout (KO) increased compliance of regenerated aortas and reduced extracellular matrix (ECM) deposition in adventitia of the regenerated aortas. Using single cell RNA sequencing (scRNA-seq), a subset of profibrotic macrophages was found to be involved in graft fibrosis and APOE KO limited the formation of profibrotic macrophage formation during vascular regeneration. The interaction between APOE and low-density lipoprotein receptor related protein 1 (LRP1) partially mediated fibrotic differentiation of the macrophages. Profibrotic macrophages promoted graft fibrosis mainly through secretion of insulin-like growth factor-1 (IGF-1) that could support proliferation of fibroblasts. Finally, we showed that APOE knockdown in vivo using adeno-associated virus (AAV) improved the compliance of regenerated aortas and reduced ECM deposited in the adventitial areas by limiting formation of profibrotic macrophages. Collectively, these data indicate that APOE promotes the profibrotic transition of macrophages partially through LRP1, and the profibrotic macrophages increase the proliferation of fibroblasts via IGF-1. Inhibition of APOE by AAV can alleviate graft fibrosis occurring during vascular regeneration.

bioengineering↗

bioRxiv2025

Multiple Routes to Metacognitive Judgments of Working Memory in the Macaque Prefrontal Cortex

The ability to evaluate ones own memory is known as metamemory. Whether metamemory is inherent to memory strength or requires additional computation in the brain remains largely unknown. We investigated the metacognitive mechanism of working memory (WM) using two-photon calcium imaging in the prefrontal cortex of macaque monkeys, who were trained to memorize spatial sequences of varying difficulties. In some trials, after viewing the sequence, monkeys could opt out of retrieval for a smaller reward, reflecting their confidence in WM (meta-WM). We discovered that PFC neurons encoded WM strength by jointly representing the remembered locations through population coding and their associated uncertainties. This WM strength faithfully predicted the monkeys recall performance and opt-out decisions. In addition to memory strength, other factors-- trial history and arousal--encoded in baseline activity predicted opt-out decisions, serving as cues for meta-WM. We identified a code of meta-WM itself that integrated WM strength and these cues. Importantly, WM strength, cues, and meta-WM were represented in different subspaces within the same PFC population. The dynamics and geometry of PFC activity implement metacognitive computations, integrating WM strength with cues into a meta-WM signal that guides behavior.

neuroscience↗

bioRxiv2025

PW-GAN: Pseudo-Warping Field Guided GAN for Unsupervised Denoising of Fetal Brain MRI Images

Fetal brain magnetic resonance imaging is of great importance for prenatal neural disorder diagnosis. To improve signal-to-noise ratio and coverage, fetal brain MRI often uses thick-slice scanning to reduce motion artifacts and ensure image quality for single slices. Reconstructing 3D MR volumes from multiple motion-corrupted stacks of 2D slices has shown promise in imaging of moving subjects like fetal MRI. However, raw scans acquired with varying slice thicknesses present substantial disparities in quality when retrospectively reconstructed into isotropic high-resolution volumes (e.g. 0.8 mm slice thickness). In particular, thick-slice acquisitions (e.g. 5-6 mm) tend to yield suboptimal reconstruction results compared to thin-slice scans (e.g. 2-3 mm), often exhibiting residual noise, interpolation-induced artifacts, and inter-slice structural discontinuities. This challenge has highlighted the need to further reduce noise caused by reconstruction errors when the reconstructed volumes are used for downstream tasks. With the success of neural networks in computer vision, deep learning methods based on architectures such as convolutional neural networks (CNNs) and generative adversarial networks (GANs) have achieved outstanding performance in single-image denoising. Nevertheless, CNN-based methods still heavily rely on large-scale datasets comprising noisy-clean image pairs. Although unsupervised GAN variants such as CycleGAN have been developed to mitigate this dependency, the inherent variability of GAN-generated outputs often results in tiny anatomical distortions, significantly limiting the applicability of GAN-based methods. While several approaches have introduced regularizations to address this issue, they largely focus on denoising individual slices, overlooking inter-slice structural inconsistencies that arise from treating slices independently. In this work, we propose Pseudo-Warping Field Guided Unsupervised Generative Adversarial Network (PW-GAN), which formulates post-reconstruction optimization as an unpaired style transfer problem between low-quality and high-quality MRI domains. Moreover, by incorporating a pseudo-deformation field module based on optical flow estimation, our method significantly enhances inter-slice continuity in the reconstructed volumes while effectively suppressing residual noise and interpolation artifacts introduced during the reconstruction process. Evaluations on both simulated and in vivo data demonstrate that our method outperforms existing unsupervised models and achieves performance on par with several state-of-the-art supervised methods.

neuroscience↗

bioRxiv2025

Themis dominates T cell exhaustion by regulation of TCR and PD-1 signaling

T cell exhaustion is important to protect the host from immunopathology during chronic viral infection, but it also impairs T cell anti-tumor immunity1-5. A fundamental unresolved question is whether and how T cell exhaustion is determined at the onset of TCR signaling6-8. Here we report an unexpected role of Themis, a TCR-proximal signaling molecule9, in T cell exhaustion. Chronic viral infection in mice usually leads to T cell exhaustion and survival of the host. Surprisingly, Themis T-cell conditional knockout mice died from severe CD8+-dependent lung immunopathology in chronic viral infection, showing Themis importance in establishing T cell exhaustion. We found that Themis-deficient CD8+ T cells were hyperactivated at the single-cell level - producing more TNF and IFN{gamma} compared to wild-type counterparts - but defective in population-level expansion. Moreover, TCF-1 and TOX expression were inhibited in Themis-deficient CD8+ T cells, thereby impairing differentiation of exhausted T cell precursors (T-pex) and maintenance of terminally exhausted T cells (T-ex), respectively. Mechanistically, Themis initially promotes TCR signaling to induce PD-1 expression and subsequently mediates PD-1 signaling. In the latter, Themis binds to PD-1 and promotes PD-1 phosphorylation and its recruitment of SHP2, thereby acting as a negative regulator to inhibit T cell effector functions. Without Themis, the orderly regulation of TCR and PD-1 signaling, and therefore exhaustion, is disrupted. Thus, our results unequivocally demonstrate that Themis-mediated early TCR signaling plays a decisive role in T cell exhaustion and provide a novel mechanism of PD-1 signaling through Themis.

immunology↗

bioRxiv2025

A cytoskeletal scaffold promotes motile cilia assembly by regulating transition-zone integrity

Motile cilia are eukaryotic organelles with essential chemo- and mechano-sensing functions across evolution, from single cell organisms to humans. Motile cilia of the mammalian nervous, respiratory and reproductive systems are characterized by unique motility proteins to generate fluid flow essential for transporting metabolites and removing mucus. The molecular mechanism of motile cilia biogenesis remains unknown. Here, we use mouse genetics, single-molecule motility assays, proteomics, high-resolution imaging, and in situ cryo-tomography to identify mammalian KIF27, a motor protein of the Kinesin-4 family and homologue of the Hedgehog pathway regulator COS2/KIF7, as a key regulator of motile cilia assembly. We show that KIF27 promotes the integrity of the transition zone, a diffusion barrier situated at the cilium base. Loss of KIF27 causes specific and profound defects in axonemal structure and disrupts cilia beating, which collectively lead to organismal phenotypes that recapitulate primary ciliary dyskinesia. We show that the motile properties of KIF27 are dispensable for its function in motile cilia biogenesis. Instead, KIF27 acts as a microtubule scaffold to regulate the transition zone architecture and enable correct ciliary incorporation of motility-generating proteins. Given that KIF27 homologues exist in different evolutionarily lineages, we propose that the ancestral activities of KIF27/KIF7 kinesins were to form a microtubule-associated scaffold for protein-protein interactions pertinent to cilia formation and signaling. The transition-zone associated KIF27 activities may represent a general building principle for motile cilia assembly in diverse species and cell types.

developmental biology↗

bioRxiv2024

Exploring the Efficiency of Deep Graph Neural Networks for RNA Secondary Structure Prediction

Ribonucleic acid (RNA) plays a vital role in various biological processes and forms intricate secondary and tertiary structures associated with its functions. Predicting RNA secondary structures is essential for understanding the functional and regulatory roles of RNA molecules in biological processes. Traditional free-energy-based methods for predicting these structures often fail to capture complex interactions and long-range dependencies within RNA sequences. Recent advancements in machine learning, particularly with graph neural networks (GNNs), have shown promise in enhancing the ability to model the relationships between molecular sequences and their structures. This work specifically explores the efficacy of various GNN architectures in modeling RNA secondary structure. Through benchmarking the GNN methods against traditional energy-based models on standard datasets, our analysis demonstrates that GNN models improves traditional methods, offering a robust framework for accurate RNA structure prediction.

bioinformatics↗

bioRxiv2024

Three-dimension transcriptomics maps of whole mouse embryo during organogenesis

Understanding mammalian development heavily relies on classical animal models like the house mouse (Mus musculus). Advanced spatial transcriptomics has enabled biologists to break new ground in studies of molecular dynamics and cellular patterning during embryonic development with spatiotemporal resolution. To construct a comprehensive developmental trajectory, current three-dimensional (3D) spatial transcriptomic profiling leverages mouse embryos from gastrulation (E5.5) to organogenesis (E13.5) in continuity. However, a crucial phase for early organogenesis between E9.5 and E11.5 was deficient. To unveil the mystery of this stage, we present the 3D transcriptomics of mouse embryos at E9.5 and E11.5, with a widely applicable reconstruction workflow that bypasses sophisticated bioinformatic calculations. As our 3D atlas is generated at single-cell resolution, we demonstrate how organogenetic processes can be interpreted at different levels of granularity, from local cellular interactions to whole embryonic regionalization. We release the open-access database MOSTA3D (Mouse Organogenesis Spatiotemporal Transcriptomic Atlas in Three-dimensional) and hope a broader community will contribute to extending this framework from conception to senility in the near future.

developmental biology↗

bioRxiv2023

Multi-omics map revealed PPARalpha activation protecting against myocardial ischemia-reperfusion injury by maintaining cardiac metabolic homeostasis

Timely percutaneous coronary intervention is the most effective initial therapy for the acute myocardial infarction (MI). However, the mechanism in energy metabolism underlying time-dependent coronary reperfusion remains largely unknown. Here, we generated an integrative map of cardiac cells using bulk and single-nucleus RNA-seq combined with metabolomics profiling of hearts with reperfusion at distinct time points post MI in rat. We found early time reperfusion (ETR), but not late time reperfusion (LTR) reduced myocardial injury by maintaining cardiac energy homeostasis. PPAR was identified as a key regulator for maintaining fatty acid metabolism after MI/R injury. Importantly, pretreatment with FDA-approved PPAR agonist, fenofibrate, improved the transcriptional signatures, and ameliorated the function of the MI/R injured hearts, particularly in the ETR. Together, our data not only deciphered the protective effect of ETR by maintaining cardiac energy homeostasis, but also provided insights into the translational potential of PPAR activation in alleviating MI/R injury.

cell biology↗

bioRxiv2023

The ciliary MBO2 complex targets assembly of inner arm dynein b and reveals additional doublet microtubule asymmetries

Ciliary motility requires the spatiotemporal coordination of multiple dynein motors by regulatory complexes located within the 96 nm axoneme repeat. Many organisms can alter ciliary waveforms in response to internal or external stimuli, but little is known about the specific polypeptides and structural organization of complexes that regulate waveforms. In Chlamydomonas, several mutations convert the ciliary waveform from an asymmetric, ciliary-type stroke to a symmetric, flagellar-type stroke. Some of these mutations alter subunits located at the inner junction of the doublet microtubule and others alter interactions between the dynein arms and the radial spokes. These and other axonemal substructures are interconnected by a network of poorly characterized proteins. Here we re-analyze several motility mutants (mbo, fap57, pf12/pacrg) to identify new components in this network. The mbo (move backwards only) mutants are unable to swim forwards with an asymmetric waveform. Proteomics identified more than 19 polypeptides that are missing or reduced in mbo mutants, including one inner dynein arm, IDA b. Several MBO2-associated proteins are also altered in fap57 and pf12/parcg mutants, suggesting overlapping networks. Two subunits are highly conserved, coiled coil proteins found in other species with motile cilia and others contain potential signaling domains. Cryo-electron tomography and epitope tagging revealed that the MBO2 complex is found on specific doublet microtubules and forms a large, L-shaped structure that contacts the base of IDA b that interconnects multiple dynein regulatory complexes and varies in a doublet microtubule specific fashion.

cell biology↗

bioRxiv2023

Cryo-electron tomography of eel sperm flagella reveals a molecular "minimum system" for motile cilia

Cilia and flagella play a crucial role in the development and function of most eukaryotic organisms. The structural core of the flagellum, the axoneme, is conserved in most eukaryotes and careful regulation of dynein motors within the axoneme is required for proper ciliary beating. The sperm flagellum from the American eel (Anguilla rostrata) has been shown to lack many of the canonical axonemal proteins, including the radial spokes, the central pair complex, and possibly even the outer row of dynein arms, presenting a "minimal" flagellar system. Here, we present cryo-electron tomography analysis of the eel sperm flagellum. We identified two states for the eel sperm flagellum within our tomograms, narrow and wide, and found that the flagellum started narrow near the sperm head and widened distally. Subtomogram averages revealed that the eel sperm flagellum has retained remnants of the missing regulatory complexes, including a short radial spoke 3 complex, basal components of radial spokes 1 and 2, and an outer dynein arm docking complex. We also describe unique structural features of the A. rostrata sperm flagellum, such as a unique pattern of holes at the inner junction and an accessory complex located at the "outer" junction. Finally, we discuss the consequences of losing key regulatory factors for the eel sperm flagellum and hypothesize several evolutionary factors that may have led to their loss. Together, our results shed light onto the structure and function of the eel sperm axoneme and provide insight into the minimum requirements for proper ciliary beating.

cell biology↗

bioRxiv2022

RGA1 alleviates low-light-repressed pollen tube growth by improving the metabolism and allocation of sugars and energy

Low-light stress compromises photosynthetic and energy efficiency and leads to spikelet sterility; however, the effect of low-light stress on pollen tube elongation in the pistil remains poorly understood. The gene RGA1, which encodes a G subunit of the heterotrimeric G protein, enhanced low-light tolerance in rice plants at anthesis by preventing the cessation of pollen tube elongation in the pistil. The levels of reactive oxygen species were higher and the content of ATP and ATPase was lower in RGA1 mutant (d1) plants compared with wild-type and RGA1-overexpressing (OE-1) plants under low-light conditions. Energy deficits, rather than interference with signaling transduction pathways, were the main contributors to the inhibition of pollen tube elongation in the pistil by low-light stress. In this process, marked increases in the activities of acid invertase (INV), sucrose synthase (SUS), and mitochondrial respiratory electron transport chain complexes, as well as the relative expression levels of SUTs, SWEETs, SUSs, INVs, CINs, SnRK1A, and SnRk1B, were observed in OE-1 plants. INV and ATPase activators (sucrose and Na2SO3, respectively) increased spikelet fertility by improving the energy status in the pistil under low-light conditions, and the ATPase inhibitor Na2VO4 induced spikelet sterility and decreased ATPase activity. Therefore, RGA1 could alleviate the low-light stress-induced impairment of pollen tube elongation to increase spikelet fertility by promoting sucrose unloading in the pistil and improving the metabolism and allocation of energy.

plant biology↗

bioRxiv2022

Mouse primary T cell phosphotyrosine proteomics enabled by BOOST

The Broad Spectrum Optimization of Selective Triggering (BOOST) approach was recently developed to increase the quantitative depth of the tyrosine phosphoproteome by mass spectrometry-based proteomics. While BOOST has been demonstrated in the Jurkat T cell line, it has not been demonstrated in scarce mice primary T cells. Here, we show the first phosphotyrosine proteomics experiment performed in mice primary T cells using BOOST. We identify and precisely quantify more than 2,000 unique pTyr sites from more than 3,000 unique pTyr peptide PSMs using only 1 mg of protein from T cell receptor-stimulated primary T cells from mice. We further reveal the importance of the phase-constrained spectrum deconvolution method ({Phi}SDM) parameter on Orbitrap instruments that, when disabled, enhances quantitation depth, accuracy, and precision in low-abundance samples. Using samples with contrived ratios, we find that disabling {Phi}SDM allows for up to a two-fold increase in the number of statistically significant intensity ratios detected while enabling {Phi}SDM degrades quantitation, especially in low-abundance samples. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/491817v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@4a2742org.highwire.dtl.DTLVardef@57645borg.highwire.dtl.DTLVardef@17dbfacorg.highwire.dtl.DTLVardef@b2df00_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2022

Three-dimensional cilia structures from animals' closest unicellular relatives, the Choanoflagellates

In most eukaryotic organisms, cilia perform a variety of life-sustaining roles related to environmental sensing and motility. Cryo-electron microscopy has provided considerable insight into the morphology and function of ciliary structures, but studies have been limited to less than a dozen of the millions of known eukaryotic species. Ultrastructural information is particularly lacking for unicellular organisms in the opisthokont clade, leaving a sizeable gap in our understanding of cilia evolution between unicellular species and multicellular metazoans (animals). Choanoflagellates are important aquatic heterotrophs, uniquely positioned within the opisthokonts as the metazoans closest living unicellular relatives. We performed cryo-focused ion beam milling and cryo-electron tomography on cilia from the choanoflagellate species Salpingoeca rosetta. We show that the axonemal dyneins, radial spokes, and central pair complex in S. rosetta more closely resemble metazoan structures than those of unicellular organisms from other suprakingdoms. In addition, we describe unique features of S. rosetta cilia, including microtubule holes, microtubule inner proteins, and the ciliary vane: a fine, net-like extension that has been notoriously difficult to visualize using other methods. Furthermore, we report barb-like structures of unknown function on the extracellular surface of the ciliary membrane. Together, our findings provide new insights into choanoflagellate biology and cilia evolution between unicellular and multicellular opisthokonts.

cell biology↗

bioRxiv2021

RB1 loss overrides PARP inhibitor sensitivity driven by RNASEH2B loss in prostate cancer

Current targeted cancer therapies are largely guided by mutations of a single gene, which overlooks concurrent genomic alterations. Here, we show that RNASEH2B, RB1, and BRCA2, three closely located genes on chromosome 13q, are frequently deleted in prostate cancer individually or jointly. Loss of RNASEH2B confers cancer cells sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition due to impaired ribonucleotide excision repair and PARP trapping. When co-deleted with RB1, however, cells lose their sensitivity, in part, through E2F1-induced BRCA2 expression, thereby enhancing homologous recombination repair capacity. Nevertheless, loss of BRCA2 re-sensitizes RNASEH2B/RB1 co-deleted cells to PARP inhibition. Our results may explain some of the disparate clinical results from PARP inhibition due to interaction between multiple genomic alterations and support a comprehensive genomic testing to determine who may benefit from PARP inhibition. Finally, we show that ATR inhibition can disrupt E2F1-induced BRCA2 expression and overcome PARP inhibitor resistance caused by RB1 loss.

cancer biology↗

bioRxiv2021

The Isl1/Shh/Wnt5a cascade controls the invasion of myoblasts by tuning the CXCL12/CXCR4 axis during tongue morphogenesis

The migration and invasion of myoblast cells derive from the occipital somites is critical for tongue morphogenesis. However, the molecular mechanisms underlying myoblast migration and invasion remain elusive. In this study, we report that transcription factor Isl1 is required for tongue development. Loss of Isl1 in the distal mandibular epithelium results in aglossia due to the defect of myoblast cells invasion. In the absence of Isl1 expression, myoblast cells in the first branchial arch fail to migrate into the presumptive tongue primordium. Down-regulation of Shh was detected in the distal mandibular epithelium after Isl1 deletion. As a downstream target gene of Shh, Wnt5a attracts the migration of mesenchymal cells expressing chemokine ligand 12 (CXCL12). CXCL12+ mesenchymal cells in the Isl1 mutant embryo fail to migrate to the distal region but accumulate in a relatively small proximal domain of the first branchial arch. CXCL12 serves as a bidirectional cue for myoblasts that express its receptor CXCR4, attracting CXCR4+ myoblasts invasion at low concentration but repelling at high concentration. The defect in the distal migration of CXCL12+ mesenchymal cells leads to a high local concentration of CXCL12, thereby preventing the invasion of CXCR4+ myoblasts. In addition, transgenic activation of Ihh alleviates the defect in tongue development and rescues the invasion of myoblasts, corroborating the functional involvement of Hedgehog signaling in tongue development. In summary, this study provides the first line of genetic evidence for the Isl1/Shh/Wnt5a cascade to regulate myoblasts invasion by tuning the CXCL12/CXCR4 axis.

developmental biology↗

bioRxiv2021

Circadian Control of Heparan Sulfate Levels Times Phagocytosis of Amyloid Beta Aggregates

Alzheimers Disease (AD) is a neuroinflammatory disease characterized partly by the inability to clear, and subsequent build-up, of amyloid-beta (A{beta}). A{beta} clearance is regulated by several pathways and has a circadian component. However, the mechanism underlying the circadian clearance of A{beta} has not been defined. Myeloid-based phagocytosis, a key mechanism in the metabolism of A{beta}, is circadianly-regulated, presenting a potential mechanism for the circadian clearance of A{beta}. In this work, we revealed that the phagocytosis of A{beta}42 undergoes a daily oscillation that is dependent on the circadian clock. We found the circadian timing of global heparan sulfate proteoglycan (HSPG) biosynthesis was the molecular timer for the clock-controlled phagocytosis of A{beta} and that both HSPG binding and A{beta}42 aggregation were essential for this oscillation. These data highlight that circadian regulation in immune cells may play a role in the intricate relationship between the circadian clock and AD. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/442651v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@bca9b3org.highwire.dtl.DTLVardef@29575corg.highwire.dtl.DTLVardef@2673c5org.highwire.dtl.DTLVardef@7a8daa_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2021

Compensating complete loss of signal recognition particle during co-translational protein targeting by the translation speed and accuracy

Signal recognition particle (SRP) is critical for delivering co-translational proteins to the bacterial inner membrane. Previously, we identified SRP suppressors in Escherichia coli that inhibit translation initiation and elongation, which provided insights into the mechanism of bypassing the requirement of SRP. Suppressor mutations tended to be located in regions that govern protein translation under evolutionary pressure. To test this hypothesis, we re-executed the suppressor screening of SRP. Here we isolated a novel SRP suppressor mutation located in the Shine-Dalgarno sequence of the S10 operon, which partially offset the targeting defects of SRP-dependent proteins. We found that the suppressor mutation decreased the protein translation rate, which extended the time window of protein targeting. This increased the possibility of the correct localization of inner membrane proteins. Furthermore, the fidelity of translation was decreased in suppressor cells, suggesting that the quality control of translation was inactivated to provide an advantage in tolerating toxicity caused by the loss of SRP. Our results demonstrated that the inefficient protein targeting due to SRP deletion can be rescued through modulating translational speed and accuracy.

microbiology↗