Production of γ-aminobutyric acid-enriched sourdough bread using an isolated Pediococcus pentosaceus strain JC30.

A γ-aminobutyric acid (GABA)-producing strain JC30 was isolated from traditional kimchi, which was identified as Pediococcus pentosaceus by 16S rDNA sequencing. P. pentosaceus JC30 was highly tolerant to acid, bile salt, and high temperatures. The survival rate of JC30 in MRS medium (pH 2.5) for 3 h was 60.96 %. Furthermore, the survival rate of JC30 in MRS medium with 3 mg/mL bile salt for 24 h was 86.62 %. The survival rate of JC30 in MRS medium at 56 °C and 58 °C for 10 min was 97.17 % and 78.20 %, respectively. When 2 % v/v JC30 (8.0 log10 CFU/mL) was added to prepare sourdough and the sourdough was then used to make bread, the bread had a higher specific volume (5.13 ± 0.12 mL/g) and GABA content (3.32 ± 0.04 mg/g DW) than the control.

RMBase v3.0: decode the landscape, mechanisms and functions of RNA modifications.

Although over 170 chemical modifications have been identified, their prevalence, mechanism and function remain largely unknown. To enable integrated analysis of diverse RNA modification profiles, we have developed RMBase v3.0 (http://bioinformaticsscience.cn/rmbase/), a comprehensive platform consisting of eight modules. These modules facilitate the exploration of transcriptome-wide landscape, biogenesis, interactome and functions of RNA modifications. By mining thousands of epitranscriptome datasets with novel pipelines, the 'RNA Modifications' module reveals the map of 73 RNA modifications of 62 species. the 'Genes' module allows to retrieve RNA modification profiles and clusters by gene and transcript. The 'Mechanisms' module explores 23 382 enzyme-catalyzed or snoRNA-guided modified sites to elucidate their biogenesis mechanisms. The 'Co-localization' module systematically formulates potential correlations between 14 histone modifications and 6 RNA modifications in various cell-lines. The 'RMP' module investigates the differential expression profiles of 146 RNA-modifying proteins (RMPs) in 18 types of cancers. The 'Interactome' integrates the interactional relationships between 73 RNA modifications with RBP binding events, miRNA targets and SNPs. The 'Motif' illuminates the enriched motifs for 11 types of RNA modifications identified from epitranscriptome datasets. The 'Tools' introduces a novel web-based 'modGeneTool' for annotating modifications. Overall, RMBase v3.0 provides various resources and tools for studying RNA modifications.

ChIPBase v3.0: the encyclopedia of transcriptional regulations of non-coding RNAs and protein-coding genes.

Non-coding RNAs (ncRNAs) are emerging as key regulators of various biological processes. Although thousands of ncRNAs have been discovered, the transcriptional mechanisms and networks of the majority of ncRNAs have not been fully investigated. In this study, we updated ChIPBase to version 3.0 (https://rnasysu.com/chipbase3/) to provide the most comprehensive transcriptional regulation atlas of ncRNAs and protein-coding genes (PCGs). ChIPBase has identified ∼151 187 000 regulatory relationships between ∼171 600 genes and ∼3000 regulators by analyzing ∼55 000 ChIP-seq datasets, which represent a 30-fold expansion. Moreover, we de novo identified ∼29 000 motif matrices of transcription factors. In addition, we constructed a novel 'Enhancer' module to predict ∼1 837 200 regulation regions functioning as poised, active or super enhancers under ∼1300 conditions. Importantly, we constructed exhaustive coexpression maps between regulators and their target genes by integrating expression profiles of ∼65 000 normal and ∼15 000 tumor samples. We built a 'Disease' module to obtain an atlas of the disease-associated variations in the regulation regions of genes. We also constructed an 'EpiInter' module to explore potential interactions between epitranscriptome and epigenome. Finally, we designed 'Network' module to provide extensive and gene-centred regulatory networks. ChIPBase will serve as a useful resource to facilitate integrative explorations and expand our understanding of transcriptional regulation.

TP53-inducible putative long noncoding RNAs encode functional polypeptides that suppress cell proliferation.

Polypeptides encoded by long noncoding RNAs (lncRNAs) are a novel class of functional molecules. However, whether these hidden polypeptides participate in the TP53 pathway and play a significant biological role is still unclear. Here, we discover that TP53-regulated lncRNAs can encode peptides, two of which are functional in various human cell lines. Using ribosome profiling and RNA-seq approaches in HepG2 cells, we systematically identified more than 300 novel TP53-regulated lncRNAs and further confirmed that 15 of these TP53-regulated lncRNAs encode peptides. Furthermore, several peptides were validated by mass spectrometry. Ten of the novel translational lncRNAs are directly inducible by TP53 in response to DNA damage. We show that the TP53-inducible peptides TP53LC02 and TP53LC04, but not their lncRNAs, can suppress cell proliferation. TP53LC04 peptide also has a function associated with cell proliferation by regulating the cell cycle in response to DNA damage. This study shows that TP53-regulated lncRNAs can encode new functional peptides, leading to the expansion of the TP53 tumor-suppressor network and providing novel potential targets for cancer therapy.

Pol3Base: a resource for decoding the interactome, expression, evolution, epitranscriptome and disease variations of Pol III-transcribed ncRNAs.

RNA polymerase III (Pol III) transcribes hundreds of non-coding RNA genes (ncRNAs), which involve in a variety of cellular processes. However, the expression, functions, regulatory networks and evolution of these Pol III-transcribed ncRNAs are still largely unknown. In this study, we developed a novel resource, Pol3Base (http://rna.sysu.edu.cn/pol3base/), to decode the interactome, expression, evolution, epitranscriptome and disease variations of Pol III-transcribed ncRNAs. The current release of Pol3Base includes thousands of regulatory relationships between ∼79 000 ncRNAs and transcription factors by mining 56 ChIP-seq datasets. By integrating CLIP-seq datasets, we deciphered the interactions of these ncRNAs with >240 RNA binding proteins. Moreover, Pol3Base contains ∼9700 RNA modifications located within thousands of Pol III-transcribed ncRNAs. Importantly, we characterized expression profiles of ncRNAs in >70 tissues and 28 different tumor types. In addition, by comparing these ncRNAs from human and mouse, we revealed about 4000 evolutionary conserved ncRNAs. We also identified ∼11 403 tRNA-derived small RNAs (tsRNAs) in 32 different tumor types. Finally, by analyzing somatic mutation data, we investigated the mutation map of these ncRNAs to help uncover their potential roles in diverse diseases. This resource will help expand our understanding of potential functions and regulatory networks of Pol III-transcribed ncRNAs.

deepBase v3.0: expression atlas and interactive analysis of ncRNAs from thousands of deep-sequencing data.

Eukaryotic genomes encode thousands of small and large non-coding RNAs (ncRNAs). However, the expression, functions and evolution of these ncRNAs are still largely unknown. In this study, we have updated deepBase to version 3.0 (deepBase v3.0, http://rna.sysu.edu.cn/deepbase3/index.html), an increasingly popular and openly licensed resource that facilitates integrative and interactive display and analysis of the expression, evolution, and functions of various ncRNAs by deeply mining thousands of high-throughput sequencing data from tissue, tumor and exosome samples. We updated deepBase v3.0 to provide the most comprehensive expression atlas of small RNAs and lncRNAs by integrating ∼67 620 data from 80 normal tissues and ∼50 cancer tissues. The extracellular patterns of various ncRNAs were profiled to explore their applications for discovery of noninvasive biomarkers. Moreover, we constructed survival maps of tRNA-derived RNA Fragments (tRFs), miRNAs, snoRNAs and lncRNAs by analyzing >45 000 cancer sample data and corresponding clinical information. We also developed interactive webs to analyze the differential expression and biological functions of various ncRNAs in ∼50 types of cancers. This update is expected to provide a variety of new modules and graphic visualizations to facilitate analyses and explorations of the functions and mechanisms of various types of ncRNAs.

RMBase v2.0: deciphering the map of RNA modifications from epitranscriptome sequencing data.

More than 100 distinct chemical modifications to RNA have been characterized so far. However, the prevalence, mechanisms and functions of various RNA modifications remain largely unknown. To provide transcriptome-wide landscapes of RNA modifications, we developed the RMBase v2.0 (http://rna.sysu.edu.cn/rmbase/), which is a comprehensive database that integrates epitranscriptome sequencing data for the exploration of post-transcriptional modifications of RNAs and their relationships with miRNA binding events, disease-related single-nucleotide polymorphisms (SNPs) and RNA-binding proteins (RBPs). RMBase v2.0 was expanded with ∼600 datasets and ∼1 397 000 modification sites from 47 studies among 13 species, which represents an approximately 10-fold expansion when compared with the previous release. It contains ∼1 373 000 N6-methyladenosines (m6A), ∼5400 N1-methyladenosines (m1A), ∼9600 pseudouridine (Ψ) modifications, ∼1000 5-methylcytosine (m5C) modifications, ∼5100 2'-O-methylations (2'-O-Me), and ∼2800 modifications of other modification types. Moreover, we built a new module called 'Motif' that provides the visualized logos and position weight matrices (PWMs) of the modification motifs. We also constructed a novel module termed 'modRBP' to study the relationships between RNA modifications and RBPs. Additionally, we developed a novel web-based tool named 'modMetagene' to plot the metagenes of RNA modification along a transcript model. This database will help researchers investigate the potential functions and mechanisms of RNA modifications.

Matrix metalloproteinase-1 expression in breast cancer and cancer-adjacent tissues by immunohistochemical staining.

Although matrix metalloproteinase-1 (MMP-1) has been considered a factor of crucial importance for breast cancer cells invasion and metastasis, the expression of MMP-1 in different breast cancer and cancer-adjacent tissues have not been fully examined. In the present study, immunohistochemical staining was used to detect the MMP-1 expression in non-specific invasive ductal carcinoma of the breast, cancer-adjacent normal breast tissue, lymph node metastatic non-specific invasive ductal carcinoma of the breast and normal lymph node tissue. The results showed that MMP-1 expression is different in the above tissues. MMP-1 had a positive expression in normal lymph node tissue and lymph node metastatic non-specific invasive ductal carcinoma. The MMP-1 negative expression rate was only 6.1% in non-specific invasive ductal carcinoma of the breast and 2.9% in cancer-adjacent normal breast tissue respectively. MMP-1 expression is higher in non-specific invasive ductal carcinoma and lymph node metastatic non-specific invasive ductal carcinoma compared to cancer-adjacent normal breast tissue and normal lymph node tissue. In conclusion, higher expression of MMP-1 in breast cancer may play a crucial role in promoting breast cancer metastasis.