What is a canonical RNA cap?

Have you ever wondered what the term canonical within a biological or biochemical context refers to?

Let us first look at a few definitions for the term “canonical” as they relate to biological rules or procedures.

Canonical definition 1: Conforming to a general rule or acceptable procedure.


Canonical definition 2: Conforming to orthodox or recognized rules.


Canonical definition 3: Reduced to the simplest and most significant form possible without loss of generality.

This could also be interpreted as the standard rule or way for describing a molecular structure such as an RNA cap structure.

The root of this is the Canonical Theory (also named the "canonical form") which is a molecular theory developed by Joel E. Keizer and coworkers which claims to explain many physical, chemical, and biological processes in a unified and canonical way. 

Canonical Theory

Canonical RNA caps

Canonical RNA caps are caps that are part of a general common pathway in regulating mRNAs.

Similar to the following definition: The term "Canonical Pathways" refers to idealized or generalized pathways conforming to or describing common properties of a particular signaling module or pathway which may also include "specific pathways", for example, specific to tissues or cell lines.

Therefore, the term “non-canonical pathways” refers to those that deviate from the canonical paradigm or standard paradigm or describe alternative biogenesis pathways and only partially meet the classical definition, or those which are alternative, less known pathways.

However, canonical and non-canonical pathways may sometimes converge.

In general, canonical in the context of biological research refers to established pathways with common features. When researchers find a new feature in an established pathway that does not fit into the canonical model, it is referred to a non-canonical.

For example, a canonical sequence of DNA, RNA or amino acids refers to the most common choice of the base or amino acid in the sequence at each position.

Ackers & Malgor and Wang et al. review and describe differences between the “canonical Wnt signaling pathway” and the “non-canonical Wnt signaling pathway.” In this review, the non-canonical signaling is described as the pathway that is responsible for chronic metabolic diseases, possibly as a result of mutations (see figure 2 in Acker & Malgor’s publication).


Ackers I, Malgor R. Interrelationship of canonical and non-canonical Wnt signalling pathways in chronic metabolic diseases. Diab Vasc Dis Res. 2018 Jan;15(1):3-13. doi: 10.1177/1479164117738442. [PMC]

Wang L, Wang H, Duan X, Dai P, Li J. Comprehensive Analysis of the Canonical and Non-canonical Wnt Signaling Pathways in Gastric Cancer. Dig Dis Sci. 2019 Oct;64(10):2830-2842. [PubMed]

Other definitions: