Genomic DNA that resides in the nuclei of mammalian neurons can be as old as the organism itself. The life span of nuclear RNAs, which are critical for proper chromatin architecture and transcription regulation, has not been determined in adult tissues. In this work, we identified and characterized nuclear RNAs that do not turn over for at least 2 years in a subset of postnatally born cells in the mouse brain. These long-lived RNAs were stably retained in nuclei in a neural cell type–specific manner and were required for the maintenance of heterochromatin. Thus, the life span of neural cells may depend on both the molecular longevity of DNA for the storage of genetic information and also the extreme stability of RNA for the functional organization of chromatin.
Long interspersed nuclear elements safeguard neural progenitors from precocious differentiation
Tomohisha Toda,
Tracy A. Bedrosian,
Simon T. Schafer,
Michael S. Cuoco,
Sara B. Linker,
Saeed Ghassemzadeh,
Lisa Mitchell,
Jack T. Whiteley,
Nicole Novaresi, et al.
Long interspersed nuclear element-1 (L1 or LINE-1) is a highly abundant mobile genetic element in both humans and mice, comprising almost 20% of each genome. L1s are silenced by several mechanisms, as their uncontrolled expression has the potential to induce genomic instability. However, L1s are paradoxically expressed at high levels in differentiating neural progenitor cells. Using in vitro and in vivo techniques to modulate L1 expression, we report that L1s play a critical role in both human and mouse brain development by regulating the rate of neural differentiation in a reverse-transcription-independent manner.
Contact
Research Group Tomohisa Toda
Max-Planck-Zentrum für Physik und Medizin Kussmaulallee 2 91054 Erlangen, Germany
