Interactions of the Trypanosoma brucei brucei zinc-finger-domain protein ZC3H28

In Trypanosoma brucei and related Kinetoplastids, regulation of gene expression occurs mostly post-transcriptionally, and RNA-binding proteins play a critical role in the regulation of mRNA and protein abundance. Trypanosoma brucei ZC3H28 is a 114 KDa cytoplasmic mRNA-binding protein with a single C(x)(7)C(x)(5)C(x)(s)H zinc finger at the C-terminus and numerous proline-, histidine- or glutamine-rich regions. ZC3H28 is essential for normal bloodstream-form trypanosome growth, and when tethered to a reporter mRNA, ZC3H28 increased reporter mRNA and protein levels. Purification of N-terminally tagged ZC3H28 followed by mass spectrometry showed enrichment of ribosomal proteins, various RNA-binding proteins including both poly(A) binding proteins, the translation initiation complex EIF4E4/EIF4G3, and the activator MKT1. Tagged ZC3H28 was preferentially associated with long RNAs that have low complexity sequences in their 3'-untranslated regions; their coding regions also have low ribosome densities. In agreement with the tethering results, after ZC3H28 depletion, the levels of a significant proportion of its bound mRNAs decreased. We suggest that ZC3H28 is implicated in the stabilization of long mRNAs that are poorly translated.

Automated summary

In Trypanosoma brucei, ZC3H28 protein plays a vital role in stabilizing specific mRNAs and increasing protein levels. Mass spectrometry revealed that ZC3H28 is associated with ribosomal proteins, various RNA-binding proteins, and is involved in regulating long and poorly translated mRNAs.