GpppN

GpppN is a shorthand notation used in molecular biology to describe a specific 5' cap structure on RNA: guanylate triphosphate linked to the first transcribed nucleotide (N) through a 5'-5' triphosphate bridge. It denotes the non-methylated form of the cap that appears in nascent transcripts prior to maturation. The mature eukaryotic cap is usually m7GpppN, where the cap guanine carries a methyl group at the N7 position.

Biogenesis and structure: During capping, a guanylyltransferase attaches GMP to the 5' end of the nascent RNA, forming GpppN. A subsequent methyltransferase methylates the cap guanine to yield m7GpppN and often 2'-O methylates the first nucleotide, reinforcing cap function.

Function and recognition: The cap protects RNA from exonucleolytic decay, promotes splicing and nuclear export, and is essential for efficient translation initiation. Cap-binding proteins, notably eIF4E and the nuclear cap-binding complex, preferentially recognize methylated caps; non-methylated GpppN interacts more weakly and can alter translation efficiency and RNA fate.

Applications: GpppN and related cap analogs are used in in vitro transcription to generate capped RNAs for research. Comparing GpppN with methylated forms helps dissect the contributions of cap structure to stability, export, and translation.

See also: m7G cap, cap analogs, eIF4E, RNA capping.