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Protein acetylation emerged as a key regulatory mechanism for many cellular processes. We used genetic analysis of Saccharomyces cerevisiae to identify Esa1 as a histone acetyltransferase required for autophagy. We further identified the autophagy signaling component Atg3 as a substrate for Esa1. Specifically, acetylation of K19 and K48 of Atg3 regulated autophagy by controlling Atg3 and Atg8 interaction and lipidation of Atg8. Starvation induced transient K19-K48 acetylation through spatial and temporal regulation of the localization of acetylase Esa1 and the deacetylase Rpd3 on pre-autophagosomal structures (PASs) and their interaction with Atg3. Attenuation of K19-K48 acetylation was associated with attenuation of autophagy. Increased K19-K48 acetylation after deletion of the deacetylase Rpd3 caused increased autophagy. Thus, protein acetylation contributes to control of autophagy.

Prostate cancer remains one of the most prevalent cancers and the main causes of cancer-related deaths in males. Various articles introduced that long noncoding RNAs (lncRNAs) are found in vital functions in the development and progression of cancers. Although SNHG3 (small nucleolar RNA host gene 3) has been investigated in many cancers, now researches on the role and mechanism of SNHG3 in prostate cancer are lacked. In this work, SNHG3 exerted high expression in prostate cancer cell lines. Suppression of SNHG3 inhibited cell proliferation, migration, EMT (epithelial-mesenchymal transition) process and promoted cell apoptosis. Additionally, it was found that SNHG3 could bind with miR-577. Subsequently, SMURF1 (Smad ubiquitination regulatory factor 1) was identified as a downstream target of miR-577 and had a negative correlation with miR-577. SNHG3 was found to positively regulate SMURF1 expression. Furthermore, rescue assays demonstrated that cotransfection of pcDNA3.1/SMURF1 reversed the effects of SNHG3 knockdown in cell proliferation, migration, EMT process and cell apoptosis. SNHG3 also promoted tumorigenesis in vivo. All the results above explained that SNHG3 accelerated prostate cancer progression by sponging miR-577 to up-regulate SMURF1 expression, suggesting that SNHG3 may act as a biomarker for prostate cancer patients. K E Y W O R D SmiR-577, prostate cancer, SMURF1, SNHG3

Cells mitigate ER stress through the unfolded protein response (UPR). Here, we report formation of ER whorls as an effector mechanism of the ER stress response. We found that strong ER stress induces formation of ER whorls, which contain ER-resident proteins such as the Sec61 complex and PKR-like ER kinase (PERK). ER whorl formation is dependent on PERK kinase activity and is mediated by COPII machinery, which facilitates ER membrane budding to form tubular-vesicular ER whorl precursors. ER whorl precursors then go through Sec22b-mediated fusion to form ER whorls. We further show that ER whorls contribute to ER stress-induced translational inhibition by possibly modulating PERK activity and by sequestering translocons in a ribosome-free environment. We propose that formation of ER whorls reflects a new type of ER stress response that controls inhibition of protein translation.

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Background Long noncoding RNAs (lncRNAs) are involved in the tumorigenesis and progression of human cancers, including renal cell carcinoma (RCC). Small nucleolar RNA host gene 4 (SNHG4) is reported to play an essential role in tumor growth and progression. However, the molecular mechanisms and function of SNHG4 in RCC remain undocumented. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine expression levels of SNHG4 in RCC tissue samples and cell lines. Cell counting kit-8, western blotting, activities of caspase-3, -8, and -9, wound-healing, and transwell invasion assays were performed to explore cell proliferation, apoptosis, migration, and invasion. The interaction among SNHG4, miR-204-5p, and RUNX2 was verified by bioinformatic analysis, a luciferase gene report, qRT-PCR, western blot analysis, and RNA immunoprecipitation assays. Xenograft mouse models were carried out to examine the role of SNHG4 in RCC in vivo. Results SNHG4 was highly expressed in RCC tissue samples and cell lines, and its upregulation was significantly involved in node involvement, distant metastasis, and reduced overall and relapse-free survival of patients with RCC. SNHG4 acted as an oncogenic lncRNA with promoted RCC cell proliferation, migration, invasion, and inhibited apoptosis. SNHG4 boosted tumor growth in xenograft mouse models. Mechanistically, SNHG4 functioned as a competing endogenous RNA (ceRNA) for sponging miR-204-5p, leading to the upregulation of its target RUNX2 to promote RCC cell proliferation and invasion. Conclusion SNHG4 and miR-204-5p might be indicated in RCC progression via RUNX2, suggesting the potential use of SNHG4/miR-204-5p/RUNX2 axis in RCC treatment.

Previous studies have reported abnormal amplitude of low-frequency fluctuation and regional homogeneity in patients with migraine without aura using resting-state functional magnetic resonance imaging. However, how whole brain functional connectivity pattern homogeneity and its corresponding functional connectivity changes in patients with migraine without aura is unknown. In the current study, we employed a recently developed whole brain functional connectivity homogeneity (FcHo) method to identify the voxel-wise changes of functional connectivity patterns in 21 patients with migraine without aura and 21 gender and age matched healthy controls. Moreover, resting-state functional connectivity analysis was used to reveal the changes of corresponding functional connectivities. FcHo analyses identified significantly decreased FcHo values in the posterior cingulate cortex (PCC), thalamus (THA), and left anterior insula (AI) in patients with migraine without aura compared to healthy controls. Functional connectivity analyses further found decreased functional connectivities between PCC and medial prefrontal cortex (MPFC), between AI and anterior cingulate cortex, and between THA and left precentral gyrus (PCG). The functional connectivities between THA and PCG were negatively correlated with pain intensity. Our findings indicated that whole brain FcHo and connectivity abnormalities of these regions may be associated with functional impairments in pain processing in patients with migraine without aura.