The multi PAM 2 protein Upa2 functions as novel core component of endosomal mRNA transport

Abstract

mRNA transport determines spatiotemporal protein expression. Transport units are higher‐order ribonucleoprotein complexes containing cargo mRNAs, RNA‐binding proteins and accessory proteins. Endosomal mRNA transport in fungal hyphae belongs to the best‐studied translocation mechanisms. Although several factors are known, additional core components are missing. Here, we describe the 232 kDa protein Upa2 containing multiple PAM2 motifs (poly[A]‐binding protein [Pab1]‐associated motif 2) as a novel core component. Loss of Upa2 disturbs transport of cargo mRNAs and associated Pab1. Upa2 is present on almost all transport endosomes in an mRNA‐dependent manner. Surprisingly, all four PAM2 motifs are dispensable for function during unipolar hyphal growth. Instead, Upa2 harbours a novel N‐terminal effector domain as important functional determinant as well as a C‐terminal GWW motif for specific endosomal localisation. In essence, Upa2 meets all the criteria of a novel core component of endosomal mRNA transport and appears to carry out crucial scaffolding functions.

The STRIPAK signaling complex regulates dephosphorylation of GUL1, an RNA-binding protein that shuttles on endosomes

“…Intriguingly, we also identified numerous potential RNA-binding proteins as targets of STRIPAK, thus suggesting extensive regulation of spatio-temporal gene expression by STRIPAK at the posttranscriptional level. Among the candidates were Pab1 (SMAC_03445), a poly(A)-binding protein that shuttles on endosomes [56], as well as GUL1, a regulator of fungal morphogenesis [25,28].…”

“…septins for endosomal assembly [60][61][62]. Transport mRNPs are stabilized by the scaffold protein Upa2 and linked to endosomes via the FYVE domain protein Upa1 [51,56]. A phylogenetic analysis revealed that important core components of endosomal transport like Upa2 and the key RBP Rrm4 are missing in ascomycetes [52].…”

Walking the line: mechanisms underlying directional mRNA transport and localisation in neurons and beyond

“…In this case, mRNA transport seems to drive not only asymmetric localisation of mRNAs to support site-specific protein synthesis, but may also play additional roles, such as enabling the efficient assembly of protein complexes in situ. Such [116]. b Endosomal/lysosomal hitchhiking in neurons.…”

“…Its deletion causes a 50% reduction in the number of processively-moving mRNAs and causes defects in hyphal growth. This protein is thought to act as a scaffold stabilising the RNA granule complex during transport [ 116 ].

Fig.

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“…Pab1 stands for poly-A binding protein. Diagram of RNA granule is adapted from [ 116 ]. b Endosomal/lysosomal hitchhiking in neurons.…”