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Dr. Marina Chekulaeva

Portrait of Marina Chekulaeva

RNA Metabolism in Neurons and Neurodegeneration Group

The Chekulaeva Group focuses on the molecular mechanisms regulating subcellular RNA localization, translation, and stability in neurons, as well as neurodegeneration, and the roles of RNA-binding proteins (RBPs) and microRNAs (miRNAs) in these processes. The neuron is a highly polarized cell, consisting of the cell body (soma) and neurite extensions (axons and dendrites). This polarity is crucial for neuronal function and relies on the asymmetric subcellular translation and localization of RNAs and proteins. The lab focuses on the identification of new cis-regulatory elements and RBPs responsible for RNA localization and seeks to understand how these processes malfunction in neurodegeneration, particularly in ALS (Amyotrophic lateral sclerosis) and CMT (Charcot-Marie-Tooth disease).

  • RNA biology and omics methods
    • Ribo-seq
    • CLIP-seq
    • SLAM-seq
    • Other transcriptomic methods
    • Polysome profiling
    • in vitro translation systems
  • hiPSC-based neuronal differentiation systems
  • Mouse primary cortical neuron cultures
  • Various imaging techniques

Current position

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Positions held 

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Academic Education

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Honors/Awards/Fellowships

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DFG-funded projects

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Selected activities

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Selected publications

  • Loedige I, Baranovskii A, Mendonsa S, Dantsuji S, Popitsch N, Breimann L, Zerna N, Cherepanov V, Milek M, Ameres S, Chekulaeva M. mRNA stability and m6A are major determinants of subcellular mRNA localization in neurons. Mol Cell. 2023 Aug 3;83(15):2709-2725.e10. doi: 10.1016/j.molcel.2023.06.021.
    Here we demonstrate that mRNA stability — rather than the presence of specific sequences, or zipcodes — is a reliable predictor for mRNA localization to neurites, especially for housekeeping mRNAs. 
  • Mendonsa S, von Kügelgen N, Dantsuji S, Ron M, Breimann L, Baranovskii A, Lödige I, Kirchner M, Fischer M, Zerna N, Bujanic L, Mertins P, Ulitsky I, Chekulaeva M. Massively parallel identification of mRNA localization elements in primary cortical neurons. Nat Neurosci. 2023 Mar;26(3):394-405. doi: 10.1038/s41593-022-01243-x.
    How do neuronal RNAs find their way to their final destination? Here we describe neuronal zipcode identification protocol (N-zip). This method can map sequences mediating RNA localization - zipcodes - across hundreds of mRNAs. Our work identifies let-7 binding site and (AU)n motif as de novo zipcodes in primary cortical neurons.
  • Mendonsa S, von Kuegelgen N, Bujanic L, Chekulaeva M. Charcot-Marie-Tooth mutation in glycyl-tRNA synthetase stalls ribosomes in a pre-accommodation state and activates integrated stress response. Nucleic Acids Res. 2021 Sep 27;49(17):10007-10017. doi: 10.1093/nar/gkab730.
    Toxic gain-of-function mutations in aminoacyl-tRNA synthetases cause neurodegeneration, known as Charcot–Marie–Tooth (CMT) disease. Here we use high-resolution ribosome profiling and interaction studies to show that CMT mutations in glycyl-tRNA synthetase deplete the pool of glycyl-tRNAGly available for translation and cause ribosomes to pause at glycine codons, which in turn activates the integrated stress response (ISR). Thus, providing a supply tRNAGly and inhibition of ISR emerge as therapeutic strategies to alleviate degeneration in CMT.
  • Ciolli Mattioli C, Rom A, Franke V, Imami K, Arrey G, Terne M, Woehler A, Akalin A, Ulitsky I, Chekulaeva M. Alternative 3' UTRs direct localization of functionally diverse protein isoforms in neuronal compartments. Nucleic Acids Res. 2019 Mar 18;47(5):2560-2573. doi: 10.1093/nar/gky1270.
    RNA localization is mediated by specific cis-regulatory elements usually found in mRNA 3'UTRs. Therefore, processes that generate alternative 3'UTRs – alternative splicing and polyadenylation – have the potential to diversify mRNA localization patterns in neurons. Here we showed that usage of alternative 3'UTRs serves as a novel mechanism mediating localization of functionally distinct protein isoforms to different subcellular compartments.
  • Zappulo A, van den Bruck D, Ciolli Mattioli C, Franke V, Imami K, McShane E, Moreno-Estelles M, Calviello L, Filipchyk A, Peguero-Sanchez E, Müller T, Woehler A, Birchmeier C, Merino E, Rajewsky N, Ohler U, Mazzoni EO, Selbach M, Akalin A, Chekulaeva M. RNA localization is a key determinant of neurite-enriched proteome. Nat Commun. 2017 Sep 19;8:583. doi: 10.1038/s41467-017-00690-6.
    The subcellular localization of proteins is fundamental to neuronal growth and synaptic plasticity which is the basis of learning and memory. Protein localization can be achieved (1) by transporting proteins as parts of RNPs or vesicular organelles; (2) through mRNA localization and local translation; or (3) via local translation of equally distributed mRNAs. While specific examples for these mechanisms have been described in the literature, it was unclear how much each of these mechanisms contributes to the overall asymmetry of protein distribution in neurons. To fill in this gap, we developed neuron fractionation scheme in combination with mass spectrometry, RNAseq, Riboseq and bioinformatics analyses to identify proteins and RNAs that are differentially localized and translated between neurites and soma. This analysis resulted in two key messages: (1) almost half on the neurite-enriched proteome is encoded by neurite-localized mRNAs, revealing mRNA localization as a key determinant of protein localization to neurites; (2) we generated a unique resource of local neuronal transcriptome, proteome and translatome and identified dozens of neurite-targeted non-coding RNAs and RNA-binding proteins with potential regulatory roles in neuronal polarity.