DNA and histone modifications exhibit noticeable impacts on gene expression 1 . Being the most prevalent internal modification in mRNA, N 6 -Methyladenosine (m 6 A) mRNA modification emerges as an important post-transcriptional mechanism of gene regulation 2 - 4 and plays critical roles in various normal and pathological bioprocesses 5 - 12 . However, how m 6 A is precisely and dynamically deposited in the transcriptome remains elusive. Here we report that H3K36me3 histone modification, a marker for transcription elongation, globally guides m 6 A modification. We found that m 6 A modifications enrich in the vicinity of H3K36me3 peaks, and are reduced globally when cellular H3K36me3 is depleted. Mechanistically, H3K36me3 is recognized and bound directly by METTL14, a critical component of the m 6 A methyltransferase complex (MTC), which in turn facilitates the binding of the m 6 A MTC to adjacent RNA polymerase II, and thereby delivering the m 6 A MTC to actively transcribed nascent RNAs to deposit m 6 A co-transcriptionally. In mouse embryonic stem cells, phenocopying Mettl14 silencing, H3K36me3 depletion also induces m 6 A reduction transcriptome-wide and in pluripotency transcripts, resulting in increased cell stemness. Collectively, our studies reveal the critical roles of H3K36me3 and METTL14 in determining precise and dynamic m 6 A deposition in mRNA, and uncover another layer of gene expression regulation involving crosstalk between histone modification and RNA methylation.

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Long non-coding RNAs (lncRNA) are classified as a kind of RNA, which are longer than 200 nucleotides in length and cannot be translated into proteins. Multiple studies have demonstrated that lncRNAs are involved in various cellular processes, including proliferation, differentiation, cell death, and metastasis. In addition, aberrant expression of lncRNAs has been discovered in human tumors, where they function as either oncogenes or tumor suppressor genes. Among numerous lncRNAs, we focus on ZNFX1 antisense RNA 1 (ZFAS1), a well-known lncRNA that is aberrant overexpression in various tumors, including melanoma, esophageal squamous cell carcinoma, non-small cell lung cancer, gastric cancer, colon cancer, and Hepatocellular carcinoma, in which it functions as oncogene. In contrast, ZFAS1 is downregulated in breast cancer, which may function as tumor suppressor gene. In this review, we provide an overview of current evidence concerning the role and potential clinical utilities of ZFAS1 in human cancers.