MBLAC1

Model summary

A soluble human endoribonuclease that uses a metallo-β-lactamase catalytic core to coordinate divalent metal ions and cleave phosphodiester bonds in structured RNA. By shuttling between nucleus and cytoplasm, it supports histone mRNA biogenesis and broader RNA maturation pathways that sustain nucleolar function and promote entry into S phase. Its metal-dependent hydrolysis mechanism positions it as a regulatory node that links RNA processing to cell-cycle control.

Predicted Gene Ontology terms

1. 01

   I begin with the InterPro architecture.

   The polypeptide is covered end-to-end by IPR036866 (Ribonuclease Z/Hydroxyacylglutathione hydrolase-like homologous superfamily, residues 1–239), which establishes a metallo-β-lactamase (MBL) fold scaffold commonly used for metal-dependent hydrolysis of phosphoester bonds. Nested within this scaffold is IPR001279 (Metallo-beta-lactamase domain, residues 66–231), the catalytic core that coordinates divalent metal ions and positions water for nucleophilic attack on phosphodiester linkages. The entire sequence is further classified by IPR039344 (Metallo-beta-lactamase domain-containing protein 1 family, residues 2–243), which narrows the functional class to an MBL-domain nuclease specialized in RNA pathways. The ordered layout—an N-terminal MBL-like superfamily envelope, a central MBL catalytic domain, and a family-level classifier—causally dictates a metal-dependent endonucleolytic mechanism.

2. 02

   This MBL architecture enforces two molecular functions.

   First, the metal-coordination chemistry inherent to IPR001279 requires divalent cations, directly supporting GO:0046872 metal ion binding. Second, the catalytic geometry of the MBL fold and its placement in an RNase Z/HYL-like superfamily drive phosphodiester cleavage within RNA, aligning with GO:0004521 RNA endonuclease activity. Together, these features specify a metal-activated endoribonuclease that trims or processes structured RNA.

3. 03

   From these molecular activities, the biological processes follow.

   An MBL endoribonuclease that operates on structured RNAs naturally feeds into RNA maturation pathways. The explicit coupling of an MBL nuclease with histone-pathway RNA metabolism points to histone mRNA biogenesis, which is formalized as GO:0008334 histone mRNA metabolic process. The enzyme’s endonucleolytic trimming and surveillance roles in RNA maturation can relieve nucleolar stress and stabilize RNA-processing assemblies, which mechanistically supports GO:1900087 positive regulation of G1/S transition of the mitotic cell cycle: by sustaining ribosome biogenesis and histone mRNA flux, the cell commits to S-phase entry.

4. 04

   Cellular localization emerges from the need to access both nuclear RNA-processing hubs and cytoplasmic RNA pools.

   The soluble MBL nuclease lacks transmembrane features and therefore partitions between compartments where RNA metabolism is active. Its participation in nucleolar pathways and histone mRNA handling argues for nuclear residence (GO:0005634 nucleus), while its broader RNA surveillance and decay roles require cytoplasmic access (GO:0005737 cytoplasm). This nucleocytoplasmic distribution is consistent with a shuttling endoribonuclease that coordinates nuclear and cytoplasmic RNA pathways.

5. 05

   Mechanistically, the protein likely binds divalent metal ions (e.g., Zn2+) within the MBL active site to activate water for endonucleolytic cleavage of structured RNA precursors and intermediates.

   In the nucleus, it probably engages histone mRNA machinery and nucleolar assembly factors to maintain ribosome biogenesis and histone transcript homeostasis. In the cytoplasm, it may interface with RNA surveillance and decay modules to fine-tune mRNA pools. I hypothesize transient assemblies with nuclear cap-binding and histone mRNP complexes (CBP20/CBP80), the U7 snRNP and Lsm1–7 pathway that governs histone mRNA turnover, nucleolar ribosome biogenesis factors (e.g., fibrillarin and nucleolin), and cytoplasmic RNA decay machinery (e.g., the RNA exosome and decapping factors). These partnerships would couple metal-dependent RNA cleavage to cell-cycle entry by stabilizing RNA-processing networks that gate the G1/S transition.