CCCH

CCCH refers to a subclass of zinc finger motifs characterized by three cysteine residues and one histidine coordinating a zinc ion. The canonical CCCH motif is often described as C-X8-C-X5-C-X3-H, with some variation in spacing, and proteins may contain one or several CCCH motifs in tandem.

These domains are found in a broad range of eukaryotic proteins, especially RNA-binding proteins and regulators of gene expression. Unlike C2H2 zinc fingers, which frequently bind DNA, CCCH-type motifs commonly interact with RNA and influence mRNA stability, localization, or translation by recruiting ribonucleases or deadenylases.

Well-characterized CCCH proteins include the TIS11 family (ZFP36/TTP and its paralogs ZFP36L1, ZFP36L2), which bind AU-rich elements in 3' untranslated regions and promote mRNA decay via the CCR4-NOT deadenylase complex. Other examples are ZAP (ZC3HAV1), which contains four CCCH motifs and has antiviral activity, and MCPIP1 (ZC3H12A), an endoribonuclease involved in inflammatory mRNA decay. Numerous CCCH-containing proteins influence development, stress responses, immunity, and metabolism across plants and animals.

Research into CCCH-type zinc fingers continues to reveal their diverse roles in post-transcriptional regulation and signal transduction. Variants and tandem repeats, as well as context within larger proteins, determine specific RNA targets and regulatory pathways.