Nephronophthisis gene products display RNA-binding properties and are recruited to stress granules

Sci Rep. 2020 Sep 29;10(1):15954. doi: 10.1038/s41598-020-72905-8.


Mutations of cilia-associated molecules cause multiple developmental defects that are collectively termed ciliopathies. However, several ciliary proteins, involved in gating access to the cilium, also assume localizations at other cellular sites including the nucleus, where they participate in DNA damage responses to maintain tissue integrity. Molecular insight into how these molecules execute such diverse functions remains limited. A mass spectrometry screen for ANKS6-interacting proteins suggested an involvement of ANKS6 in RNA processing and/or binding. Comparing the RNA-binding properties of the known RNA-binding protein BICC1 with the three ankyrin-repeat proteins ANKS3, ANKS6 (NPHP16) and INVERSIN (NPHP2) confirmed that certain nephronophthisis (NPH) family members can interact with RNA molecules. We also observed that BICC1 and INVERSIN associate with stress granules in response to translational inhibition. Furthermore, BICC1 recruits ANKS3 and ANKS6 into TIA-1-positive stress granules after exposure to hippuristanol. Our findings uncover a novel function of NPH family members, and provide further evidence that NPH family members together with BICC1 are involved in stress responses to maintain tissue and organ integrity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ankyrin Repeat
  • Carrier Proteins / metabolism
  • Cilia / metabolism
  • Ciliopathies / metabolism
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Kidney / metabolism
  • Kidney Diseases, Cystic / congenital
  • Kidney Diseases, Cystic / metabolism
  • Kidney Diseases, Cystic / physiopathology
  • Mutation
  • Nuclear Proteins / metabolism
  • Polycystic Kidney Diseases / genetics
  • RNA / metabolism
  • RNA-Binding Proteins / metabolism*
  • Sterols / pharmacology
  • Stress, Physiological / physiology*
  • Transcription Factors / metabolism


  • ANKS3 protein, human
  • ANKS6 protein, human
  • Bicc1 protein, human
  • Carrier Proteins
  • INVS protein, human
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Sterols
  • Transcription Factors
  • hippuristanol
  • RNA

Supplementary concepts

  • Nephronophthisis 2
  • Nephronophthisis, familial juvenile