7SOU

LaM domain of human LARP1 in complex with AAAAAA polynucleotide

Summary for 7SOU

• Entry DOI: 10.2210/pdb7sou/pdb
• Related: 7SOO 7SOP 7SOQ 7SOR 7SOS 7SOT
• Descriptor: Isoform 2 of La-related protein 1, RNA (5'-R(P*AP*AP*AP*AP*AP*A)-3') (3 entities in total)
• Functional Keywords: winged helix fold, rna binding domain, rna binding protein, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 13736.78

Authors

Kozlov, G.,Gehring, K. (deposition date: 2021-11-01, release date: 2022-08-03, Last modification date: 2023-10-18)

Primary citation

Kozlov, G.,Mattijssen, S.,Jiang, J.,Nyandwi, S.,Sprules, T.,Iben, J.R.,Coon, S.L.,Gaidamakov, S.,Noronha, A.M.,Wilds, C.J.,Maraia, R.J.,Gehring, K.
Structural basis of 3'-end poly(A) RNA recognition by LARP1.
Nucleic Acids Res., 50:9534-9547, 2022

PubMed Abstract: La-related proteins (LARPs) comprise a family of RNA-binding proteins involved in a wide range of posttranscriptional regulatory activities. LARPs share a unique tandem of two RNA-binding domains, La motif (LaM) and RNA recognition motif (RRM), together referred to as a La-module, but vary in member-specific regions. Prior structural studies of La-modules reveal they are pliable platforms for RNA recognition in diverse contexts. Here, we characterize the La-module of LARP1, which plays an important role in regulating synthesis of ribosomal proteins in response to mTOR signaling and mRNA stabilization. LARP1 has been well characterized functionally but no structural information exists for its La-module. We show that unlike other LARPs, the La-module in LARP1 does not contain an RRM domain. The LaM alone is sufficient for binding poly(A) RNA with submicromolar affinity and specificity. Multiple high-resolution crystal structures of the LARP1 LaM domain in complex with poly(A) show that it is highly specific for the RNA 3'-end, and identify LaM residues Q333, Y336 and F348 as the most critical for binding. Use of a quantitative mRNA stabilization assay and poly(A) tail-sequencing demonstrate functional relevance of LARP1 RNA binding in cells and provide novel insight into its poly(A) 3' protection activity.

PubMed: 35979957
DOI: 10.1093/nar/gkac696

Experimental method

X-RAY DIFFRACTION (1.45 Å)