Dynamic RNA Modifications in Gene Expression Regulation

N6-methyladenosine (m6A) is the most prevalent modification in eukaryotic messenger RNAs (mRNAs) and is interpreted by its readers, such as YTH domain-containing proteins, to regulate mRNA fate. Here, we report the insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs; including IGF2BP1/2/3) as a distinct family of m6A readers that target thousands of mRNA transcripts through recognizing the consensus GG(m6A)C sequence. In contrast to the mRNA-decay-promoting function of YTH domain-containing family protein 2, IGF2BPs promote the stability and storage of their target mRNAs (for example, MYC) in an m6A-dependent manner under normal and stress conditions and therefore affect gene expression output. Moreover, the K homology domains of IGF2BPs are required for their recognition of m6A and are critical for their oncogenic functions. Thus, our work reveals a different facet of the m6A-reading process that promotes mRNA stability and translation, and highlights the functional importance of IGF2BPs as m6A readers in post-transcriptional gene regulation and cancer biology.

Recognition of RNA N 6 -methyladenosine by IGF2BP proteins enhances mRNA stability and translation

Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis

The recent discovery of reversible mRNA methylation has opened a new realm of post-transcriptional gene regulation in eukaryotes. The identification and functional characterization of proteins that specifically recognize RNA N6-methyladenosine (m6A) unveiled it as a modification that cells utilize to accelerate mRNA metabolism and translation. N6-adenosine methylation directs mRNAs to distinct fates by grouping them for differential processing, translation and decay in processes such as cell differentiation, embryonic development and stress responses. Other mRNA modifications, including N1-methyladenosine (m1A), 5-methylcytosine (m5C) and pseudouridine, together with m6A form the epitranscriptome and collectively code a new layer of information that controls protein synthesis.

/pdf/post-transcriptional-gene-regulation-by-mrna-modifications-5984s6cty9.pdf

Post-transcriptional gene regulation by mRNA modifications

Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing.

The role of Fat Mass and Obesity-associated protein (FTO) and its substrate N6-methyladenosine (m6A) in mRNA processing and adipogenesis remains largely unknown. We show that FTO expression and m6A levels are inversely correlated during adipogenesis. FTO depletion blocks differentiation and only catalytically active FTO restores adipogenesis. Transcriptome analyses in combination with m6A-seq revealed that gene expression and mRNA splicing of grouped genes are regulated by FTO. M6A is enriched in exonic regions flanking 5′- and 3′-splice sites, spatially overlapping with mRNA splicing regulatory serine/arginine-rich (SR) protein exonic splicing enhancer binding regions. Enhanced levels of m6A in response to FTO depletion promotes the RNA binding ability of SRSF2 protein, leading to increased inclusion of target exons. FTO controls exonic splicing of adipogenic regulatory factor RUNX1T1 by regulating m6A levels around splice sites and thereby modulates differentiation. These findings provide compelling evidence that FTO-dependent m6A demethylation functions as a novel regulatory mechanism of RNA processing and plays a critical role in the regulation of adipogenesis.

/pdf/fto-dependent-demethylation-of-n6-methyladenosine-regulates-292e7wgwq9.pdf

FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis

To investigate the preservative effect of composite biopreservatives on goat meat during chilled storage, three biopreservatives (chitosan, tea polyphenols and grape seed extract) were selected. Meat samples were soaked in composite biopreservatives at previously optimized concentrations, prior to storage at 4 °C for 12 days. Meat quality parameters including pH, TBARS, TVB-N, color, sensory index and total viable count were evaluated. 16S rDNA high-throughput sequencing combined with bioinformatics was used to assess the changes in the bacterial community, while molecular docking permitted the investigation of molecular interaction between gyrase, catechins, and anthocyanins. Treatment by composite biopreservatives contributed to the stability and maintenance of meat quality, notably by significantly reducing TBARS and maintaining meat color and sensory scores. Pseudomonadales, Bacillales and Flavobacteriales were effectively inhibited as the main spoilage bacteria in goat meat during chilled storage. Molecular docking revealed that catechins and anthocyanins could bind to DNA gyrase by hydrogen bonds and hydrophobic interactions, thus inhibiting DNA synthesis and bacterial growth. Hence, the composite biopreseratives exerted a preservative impact on the chilled goat meat. 

Preservative effects of composite biopreservatives on goat meat during chilled storage: Insights into meat quality, high-throughput sequencing and molecular docking

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FTO-dependent demethylation of N6-methyladenosine regulates mRNA splicing and is required for adipogenesis

Preservative effects of composite biopreservatives on goat meat during chilled storage: Insights into meat quality, high-throughput sequencing and molecular docking