Gene Expression

Gene expression is the process by which information encoded in DNA is converted into functional products, chiefly proteins, that underlie cellular phenotype. It begins with transcription, in which RNA polymerase locates a promoter and synthesises a messenger RNA (mRNA) transcript; this primary transcript is then processed by capping, splicing and polyadenylation, before export to the cytoplasm. There, ribosomes initiate translation at a start codon and elongate the polypeptide chain until a stop codon is reached. Beyond this core pathway, expression is regulated at multiple points: chromatin structure dictates promoter accessibility, transcription factors and cofactors control initiation, alternative splicing generates multiple protein isoforms, mRNA stability and small-RNA-mediated silencing modulate transcript abundance, and post-translational modifications of proteins fine-tune activity. Together, these layers permit tissue-specific, developmental and environmental responses, ensuring that each cell type deploys an appropriate complement of proteins in time and space.

Research from Nature Portfolio

Studies employing genomic and structural approaches have begun to reveal the detailed mechanisms that coordinate transcription with chromatin and DNA repair. A novel double-DAP-seq method has mapped genome-wide binding sites of bZIP transcription-factor heterodimers in Arabidopsis, demonstrating that heterodimer formation greatly broadens DNA-binding specificity beyond homodimers, and uncovering distinct recognition of ACGT motifs that underlie combinatorial control of stress and developmental genes. High-resolution cryo-EM structures of human RNA polymerase II in complex with transcription-coupled repair factors have elucidated how factors such as ELOF1 and UVSSA position ubiquitin ligases to modify Pol II upon stalling, thereby directing TFIIH engagement and coordinating lesion excision with transcription restart. In parallel, genome-wide profiling of trabectedin-induced DNA adducts in cancer cells has shown that abortive repair of these lesions by transcription-coupled nucleotide excision repair generates persistent single-strand breaks in highly transcribed regions, linking gene expression levels directly to DNA-damage hotspots and suggesting new avenues for precision oncology.

Research from all publishers

Diverse advances outside the portfolio have highlighted the dynamic regulation of transcriptomes by non-coding RNAs and genetic variation. A novel co-expression network framework applied to prostate cancer has revealed that isomiRs—miRNA length and sequence variants—undergo tumour-specific rewiring, with loss of normal negative correlations between highly expressed isomiRs and their mRNA targets in cancer, pointing to global deregulation of post-transcriptional control. Functional studies of A-to-I RNA editing in prostate cell lines have demonstrated that editing of miR-379 alters its tumour-suppressive activity and target-gene networks, establishing a paradigm for recoding-driven modulation of gene expression. Moreover, mapping of cis-acting single-nucleotide polymorphisms within precursor miRNA regions has shown that common variants shape isomiR repertoires in human tissues, providing a direct link between genetic variation and post-transcriptional regulatory diversity.

Gene Expression publication trend

The graph below shows the total number of articles in gene expression across all publications each year (not limited to Nature Index journals).

Technical terms

Promoter: A DNA region, typically located upstream of a gene’s transcription start site, that binds general transcription factors and RNA polymerase to initiate transcription.

Enhancer: A distal DNA element that binds sequence-specific transcription factors and, via DNA looping, stimulates transcription from a promoter, often in a tissue-specific manner.

Chromatin: The nucleoprotein complex of DNA and histones; its structural state (euchromatin versus heterochromatin) governs DNA accessibility and gene activity.

IsomiR: A variant form of a microRNA differing by one or more nucleotides at the 5′ or 3′ end, generated by alternative processing and capable of modulating target specificity.

Adenosine-to-inosine (A-to-I) editing: A post-transcriptional modification in which ADAR enzymes deaminate adenosine within double-stranded RNA, altering base-pairing and potentially recoding transcripts.

References

1. Double DAP-seq uncovered synergistic DNA binding of interacting bZIP transcription factors. Nature Communications (2023).
2. Structural basis of human transcription–DNA repair coupling. Nature (2021).
3. Trabectedin derails transcription-coupled nucleotide excision repair to induce DNA breaks in highly transcribed genes. Nature Communications (2024).
4. Differential co-expression network analysis with DCoNA reveals isomiR targeting aberrations in prostate cancer. Bioinformatics (2023).
5. Functional consequences of A-to-I editing of miR-379 in prostate cancer cells. Scientific Reports (2023).
6. Genetic Regulation of Human isomiR Biogenesis. Cancers (2023).