Makorin Ring Zinc Finger Protein 1 (MKRN1), a Novel Poly(A)-binding Protein-interacting Protein, Stimulates Translation in Nerve Cells

Abstract

Background: Synaptic activity induces translation of mRNAs in dendrites of neurons. Results: Makorin 1 (MKRN1) interacts with poly(A)-binding protein, stimulates translation, accumulates in neuronal dendrites after plasticity-inducing stimuli, and is associated with dendritic mRNAs. Conclusion: MKRN1 has the potential to locally control the translation of dendritic mRNAs at synapses. Significance: MKRN1 is a novel positive regulator of translation.

Integrative genomics positions MKRN 1 as a novel ribonucleoprotein within the embryonic stem cell gene regulatory network

“…Among these RBPs, we found that full‐length MKRN1 interacts with established mRNA‐binding proteins including PABPC1, PABPC4, L1TD1, and YBX1 independently of RNA (Fig C). Consistent with these data, Miroci et al (2012) reported a direct interaction between PABPC1 and recombinant MKRN1‐short isoform in HEK 293 cells . The MKRN1‐short isoform lacks the C 3 HC 4 RING domain, which Miroci et al (2012) reasoned imparts ribonucleoprotein function to the MKRN1‐short isoform rather than E3 ubiquitin ligase activity.…”

LEP-2/Makorin regulates LIN-28 stability to promote the juvenile-to-adult transition in Caenorhabditis elegans

“…Indeed, Mkrn1 in mammals functions as an E3 ligase, targeting several proteins and even itself, although has not yet been identified as one of its targets (Kim et al, 2005;Salvatico et al, 2010;Lee et al, 2009Lee et al, , 2012Ko et al, 2012;Shimada et al, 2009;Ko et al, 2010;Kim et al, 2014;Cassar et al, 2015). In other contexts, Mkrns are also RNA-binding proteins, are localized to ribonucleoprotein granules, and have been found to sequester some mRNAs or promote their translation (Cano et al, 2010;Cassar et al, 2015;Gajdos et al, 2010;Kwon et al, 2013;Miroci et al, 2012;Cheung et al, 2010;Yang et al, 2008). Thus, an alternative mechanism for LEP-2/Mkrn function could be to sequester, protect from degradation and/or promote the translation of an mRNA encoding another protein that promotes LIN-28 destruction.…”

Poly(A)-binding proteins and mRNA localization: who rules the roost?

“…Although the contribution of PABP to the regulation of localized mRNAs is not fully understood, several functions can be envisaged; it may maintain mRNA stability or may be targeted to achieve repression (e.g. during transport) and/or facilitate activitydependent translation [64][65][66][67][68]. Finally, as PABP binds the dendritic-localizer sequence of vasopressin mRNA [69], it is formally possible that it may contribute to mRNA transport.…”

“…dendrites, axonal filopodia and terminal growth cones [62,63] and co-localizes in punta/granules with RNA-binding proteins, such as the wellcharacterized HuD [64], implicated in activity-dependent localized translation, as well as with putative regulatory factors, e.g. Makorin RING zinc finger protein (MKNR)1 [65], with which it interacts. Furthermore, PABP interacts with dendritically localized regulatory RNAs, e.g.…”