Kristin Koutmou

Assistant Professor of Chemistry

Post.Doc., Howard Hughes Institute of Medicine at Johns Hopkins School of Medicine
Ph.D. Chemistry, University of Michigan, Ann Arbor
B.S., University of Colorado at Denver

Research Focus: Ribosome function and regulation

Phone: 734.764.5650
E-mail: kkoutmou@umich.edu

RWhat happens when the ribosome goes awry?

The ribosome is responsible for synthesizing proteins and its function is crucial for cellular health. Research projects in the Koutmou lab seek to uncover what happens when the ribosome encounters a problematic mRNA sequence or when the ribosome itself is dysfunctional. We take a three-pronged approach, combining the power of mechanistic enzymology, cell-based studies, and genome-wide (ribosome profiling) techniques to investigate the molecular level mechanisms of events that occur when translation is disrupted. Our work is poised to have major impact on the field by identifying and characterizing mechanisms that disrupt translation and contribute to (or cause) human disease.


Ribosome sliding during poly(A) translation.

A number of recent studies indicate that a substantial amount of premature (or alternative) polyadenylation occurs in eukaryotes; in this situation a poly(A) sequence can be inserted into an ORF upstream of a stop codon resulting in the ribosome de-coding a poly(A) tail (and never encountering a stop codon) (Fig. 1A/B). Eukaryotic cells contain an KoutmoumRNA surveillance pathway called Non-Stop-Decay (NSD) thought to be triggered when the ribosome translates a poly(A) tail. NSD is likely of considerable biological significance given the frequency with which ribosomes likely encounter poly(A) inserted into an ORF. I discovered a novel ribosome movement on poly(A) sequences that could explain why poly(A) is used in a non-coding capacity called ‘ribosome sliding (Koutmou, et al. eLife (2015)).’ Interestingly, examples of deleterious AAG to AAA synonymous point mutations that result in poly(A) sequences are found disproportionately in multiple human cancer cell lines (Arthur, et al. Sci Adv. (2015)). Thus, ribosome sliding may explain how some synonymous mutations influence gene expression in pathological states. We use a combination of careful kinetic and genome wide studies to investigate the biological consequences for ribosomes encountering a poly(A) sequence, and provide the biochemical framework necessary for understanding the potential contributions of ribosome sliding events to human disease.

Detection, clearance and impact of defective ribosomes.

Cells contain quality control mechanisms that survey translation (such as NSD). If translation is impeded these mechanisms sense the stall or problem (i.e. with the mRNA, protein or ribosome) and target the offending party for degradation. It is becoming apparent that many processes initially identified as ‘quality control mechanisms’ actually regulate the expression of a variety of genes. Our lab aims to define the precise contribution to biology and human health of a translation quality control called “nonfunctional rRNA decay” (NRD). NRD targets ribosomes with dysfunctional ribosomal RNAs (rRNAs) for elimination. Ribosomes containing mutations that disrupt ribosome biogenesis or function cause disorders called “ribosomopathies”. Ribosomopathies typically result from mutations in ribosomal proteins and are characterized by bone marrow failure and anemia early in life, and an increased risk of cancer in older adults. An intriguing possibility is that NRD itself plays a role in moderating the development of ribosomopathies. Our work aims to understand the role of NRD in biology (including its contributions to ribosomopathies) and reveal the mechanism of NRD.



Our awareness of the breadth and significance of situations that perturb translation has grown considerably in recent years. An emerging appreciation for the important roles of translation quality control mechanisms, coupled with the availability of diverse powerful tools (e.g. in vitro translation systems and ribosome profiling) put the work in the Koutmou lab at the forefront of understanding how disruptions in translation and translation regulation can impact cancer and disease.



  Ruth L. Kirschstein NRSA Post-Doctoral Award, NIH
  NIH Cellular Biotechnology Training Grant
  Robert W. Parry Scholarship for Summer Research at the University of Michigan


Representative Publications

  1. KS Koutmou, JL Brunelle, S Djuranovic, R Green. “Ribosomes slide on lysine-encoding homopolymeric A stretches.” eLife (2015), PMID    25695637

  2. Arthur L, Pavlovic-Djuranovic S, Koutmou KS, Green R, Szczesny P, Djuranovic S. “Translational control by lysine-encoding A-rich sequences.” Science Advances (2015), PMID 26322332

  3. KS Koutmou, ME McDonald, JL Brunelle, R Green. “RF3:GTP promotes rapid dissociation of the class 1 termination factor.” RNA (2014), PMID 24667215

  4. KS Koutmou, JJ Day-Storms, CA Fierke, “The RNR motif of B. subtilis RNase P protein interacts with both PRNA and pre-tRNA to stabilize an active conformer,” RNA (2011), PMID 21622899

  5. J Hsieh, KS Koutmou, D Rueda, M Koutmos, NG Walter, CA Fierke, “A divalent cation stabilizes the active conformation of the B. subtilis RNase P•pre-tRNA complex: a role for an inner-sphere metal ion in RNase P,” Journal of Molecular Biology (2010), PMID 20434461

  6. KS Koutmou, A Casiano-Negroni, M Getz, S Paczini, AJ Andrews, JE Penner-Hahn, HM Al-Hashimi, CA Fierke. “NMR and XAS reveal an inner-sphere metal binding site in the P4 helix of the metallo-ribozyme ribonuclease P,” Proceedings of the National Academy of Sciences (2010), PMID 20133747

  7. KS Koutmou, NH Zahler, JC Kurz, FE Campbell, ME Harris, CA Fierke. “Protein–precursor tRNA contact leads to sequence-specific recognition of 5′ leaders by bacterial ribonuclease P,” Journal of Molecular Biology (2010), PMID 19932118