The multifaceted eukaryotic cap structure

Abstract

The 5′ cap structure is added onto RNA polymerase II transcripts soon after initiation of transcription and modulates several post‐transcriptional regulatory events involved in RNA maturation. It is also required for stimulating translation initiation of many cytoplasmic mRNAs and serves to protect mRNAs from degradation. These functional properties of the cap are mediated by several cap binding proteins (CBPs) involved in nuclear and cytoplasmic gene expression steps. The role that CBPs play in gene regulation, as well as the biophysical nature by which they recognize the cap, is quite intricate. Differences in mechanisms of capping as well as nuances in cap recognition speak to the potential of targeting these processes for drug development. In this review, we focus on recent findings concerning the cap epitranscriptome, our understanding of cap binding by different CBPs, and explore therapeutic targeting of CBP‐cap interaction. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein‐RNA Recognition RNA Processing > Capping and 5′ End Modifications Translation > Translation Mechanisms

CMTR1 is recruited to transcription start sites and promotes ribosomal protein and histone gene expression in embryonic stem cells

“…For the ribosomal protein genes and histone genes, the impact of CMTR1 on transcript appeared direct; in isolated nuclei CMTR1 knockdown results in a reduction in their transcription and addition of recombinant CMTR1 increases their transcription. RNMT and its product the m7 G cap are linked to a transcriptional checkpoint involving co-transcriptional stability and protein:protein interactions ( 1 , 27 , 37 ). For CMTR1 and its product N1 2′-O-Me, it is likely that analogous influences on co-transcriptional stability and transcriptional mechanisms are governing CMTR1-dependent mRNA levels.…”

“…The RNA cap is added to the initiating nucleotide of RNA pol II (RNAPII) transcripts. It protects RNA from degradation by blocking exonucleases during transcription and identifies RNA as cellular in origin or ‘self’, protecting it from degradation by proteins of the innate immunity pathways ( 1–3 ). The most prevalent cap structure, denoted m7 GpppX m , includes 7-methylguanosine ( m7 G) and first nucleotide ribose O2-methylation (X m or N1 2′-O-Me) ( 4 , 5 ).…”

“…Following transcription initiation, a series of enzymes catalyse RNA cap formation, starting with guanosine linkage to the first transcribed nucleotide by a 5′ to 5′ triphosphate bridge ( 1 , 8 ). This cap guanosine is methylated at the N-7 position, the first and second transcribed nucleotides are methylated on the ribose at the O-2 position, and if the first nucleotide is adenosine it may also be methylated at the N-6 position ( 13 ).…”

capCLIP: a new tool to probe translational control in human cells through capture and identification of the eIF4E–mRNA interactome

“…While eIF4E +/− mice are viable, eIF4E +/− embryonic fibroblasts resist oncogenic transformation ( 5 ), indicating that cellular translational activity is acutely sensitive to levels of eIF4E. Other cap-binding proteins also exist, including eIF4E2 (4EHP) and eIF4E3, although their cellular roles remain poorly understood ( 6 ).…”

Overview of Methods for Large-Scale RNA Synthesis

“…It is also required for mRNA splicing, export and initiation of translation [82,84,85]. Therefore, capped RNAs are widely used in studies concerning vital cellular processes [86][87][88]. The increasing demand on simple and efficient methods for synthesis of capped mRNAs resulted in the development of several protocols [86,[89][90][91].…”