Nuclear speckle fusion via long-range directional motion regulates speckle morphology after transcriptional inhibition

J Cell Sci. 2019 Apr 17;132(8):jcs226563. doi: 10.1242/jcs.226563.

Abstract

Although the formation of RNA-protein bodies has been studied intensively, their mobility and how their number and size are regulated are still poorly understood. Here, we show significantly increased mobility of nuclear speckles after transcriptional inhibition, including long-range directed motion of one speckle towards another speckle, terminated by speckle fusion, over distances up to 4 µm and with velocities between 0.2 µm/min and 1.5 µm/min. Frequently, three or even four speckles follow very similar paths, with new speckles appearing along the path followed by a preceding speckle. Speckle movements and fusion events contribute to fewer, but larger, speckles after transcriptional inhibition. These speckle movements are not actin dependent, but occur within chromatin-depleted channels enriched with small granules containing the speckle marker protein SON. Similar long-range speckle movements and fusion events were observed after heat shock or heavy metal stress, and during late G2 and early prophase. Our observations suggest a mechanism for long-range, directional nuclear speckle movements, contributing to overall regulation of nuclear speckle number and size as well as overall nuclear organization. This article has an associated First Person interview with the first author of the paper.

Keywords: Interchromatin granule clusters; Nuclear bodies; Nuclear speckles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / chemistry
  • Actins / metabolism
  • Animals
  • CHO Cells
  • Chromatin / genetics
  • Chromatin / metabolism
  • Cricetulus
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Heat-Shock Response*
  • Humans
  • Intranuclear Inclusion Bodies / metabolism*
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / metabolism
  • Transcriptional Activation*
  • Transgenes*

Substances

  • Actins
  • Chromatin
  • DNA-Binding Proteins
  • Minor Histocompatibility Antigens
  • SON protein, human