1H, 13C, and 15N resonance assignments of the La Motif of the human La-related protein 1

Abstract

Human La-related protein 1 (HsLARP1) is involved in post-transcriptional regulation of certain 5' terminal oligopyrimidine (5'TOP) mRNAs as well as other mRNAs and binds to both the 5'TOP motif and the 3'-poly(A) tail of certain mRNAs. HsLARP1 is heavily involved in cell proliferation, cell cycle defects, and cancer, where HsLARP1 is significantly upregulated in malignant cells and tissues. Like all LARPs, HsLARP1 contains a folded RNA binding domain, the La motif (LaM). Our current understanding of post-transcriptional regulation that emanates from the intricate molecular framework of HsLARP1 is currently limited to small snapshots, obfuscating our understanding of the full picture on HsLARP1 functionality in post-transcriptional events. Here, we present the nearly complete resonance assignment of the LaM of HsLARP1, providing a significant platform for future NMR spectroscopic studies.

Keywords: LARP1; La motif; La-related protein; RNA-binding domain.

Figure 1:

[¹H,¹⁵N]-HSQC spectrum of 1.3 mM [¹³C,¹⁵N]-labeled HsLARP1(392–486) recorded at 700 MHz and 298 K in a buffer containing 20 mM Tris/HCl pH 7.5, 100 mM NaCl, 10% D₂O. Side chain resonances of W/N/Q are labeled with a double dagger (‡), peak splitting of L485 is indicated by an asterisk (*). ¹H^ε-¹⁵N^ε side chain resonances belonging to arginine are folded and labeled with a dagger (†).

Figure 2:

Secondary structure of HsLARP1(392–486). Chemical shifts were used to determine the α-helix propensity (shown in blue from 0 to 1) and β-strand propensity (shown in orange from 0 to −1). The amino acid sequence is shown. STRIDE was used to indicate location of α-helices, β-strands, and a 3₁₀-helix in an AlphaFold prediction of HsLARP1(392–486).