capindependent

Capindependent refers to mechanisms of translation initiation that occur without the 5' cap structure on eukaryotic mRNAs. In typical eukaryotic translation, the 5' cap is recognized by initiation factors such as eIF4E, guiding ribosomes to the start codon. Cap-independent translation uses alternative RNA elements or structures that recruit ribosomes without requiring the cap.

Main mechanisms include:

- Internal ribosome entry sites (IRES): RNA sequences within the mRNA (often in the 5' UTR) that recruit ribosomes directly to an internal start site, sometimes requiring ITAFs (IRES-trans-acting factors). Widely studied in picornaviruses; some cellular mRNAs also show IRES activity.

- Cap-independent translation elements (CITEs) in plant viruses: structural elements located in the 3' or 5' UTRs that enable ribosome recruitment through long-distance RNA–protein interactions, often circumventing the need for a cap and eIF4E.

- tRNA-like structures and other RNA motifs: certain viral RNAs possess tRNA-like structures at the termini that can mimic components of the translation apparatus to promote translation initiation.

- Other modalities: alternative initiation factors and cap-independent recruitment pathways that may use eIF4G or eIF3 in the absence of eIF4E.

Biological significance:

Cap-independent translation provides a mechanism to maintain protein synthesis when cap-dependent translation is reduced, such as during cellular stress, nutrient deprivation, or viral infection. It can enable selective translation of stress-responsive or viral proteins.

Examples and scope:

IRES elements are found in several viral RNAs, notably hepatitis C and poliovirus, and in some cellular mRNAs (e.g., c-Myc, VEGF). Plant viruses employ CITEs to promote translation of their RNAs via cap-independent routes.

Detection and controversy:

Identifying functional cap-independent elements is technically challenging; some presumed IRES activities have been attributed to experimental artefacts, and validation requires careful controls.