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bioRxiv · 10.1101/2022.09.22.508989

Anticodon-like loop-mediated dimerization in the crystal structures of HdV- like CPEB3 ribozymes

Przytula-Mally, I.·Engilberge, S.·Johannsen, S.·Olieric, V.·Masquida, B.·Sigel, R. K. O.
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Abstract

Cytoplasmic polyadenylation element-binding (CPEB) proteins are involved in many cellular processes, including cell division, synaptic plasticity, learning, and memory. A highly conserved, short mammalian ribozyme has been found within the second intron of the CPEB3 gene. Based on its cleavage mechanism and structural features, this ribozyme belongs to the hepatitis delta virus (HDV)-like ribozyme family. Here, we present the first crystallographic structures of human and chimpanzee CPEB3 ribozymes, both confirming the general topology of the HDV ribozyme with two parallel coaxial helical stacks. However, the residues involved in forming the P1.1 mini-helix, which is an integral part of the characteristic nested double pseudoknot involving P1, P2, and P3, instead participate in a seven nucleotides loop with a conformation similar to the one from the anticodon (AC) loop of tRNAs when interacting with the mRNA codon. The conformation of the loop supports the formation of a four-base pair helix by interacting with the AC-like loop from a symmetry-related ribozyme leading to ribozyme dimer formation. The present crystal structures link for the first time the sequence specificities of the CPEB3 and the HDV (genomic and antigenomic) ribozymes to their different structural features. This work corroborates the hypothesis made by Szostak that HDV ribozymes may have evolved from the CPEB3 ribozyme.

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Przytula-Mally, I., Engilberge, S., Johannsen, S., Olieric, V., Masquida, B., Sigel, R. K. O.. 2022-09-22. Anticodon-like loop-mediated dimerization in the crystal structures of HdV- like CPEB3 ribozymes. https://doi.org/10.1101/2022.09.22.508989

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