[citation needed] Guttman's research aims to understand the mechanisms by which non-coding RNAs regulate gene expression.
Guttman's work has uncovered the detailed molecular mechanisms that enable Xist to exploit 3-dimensional proximity to identify its target sites on the X chromosome, interact with the SHARP/SMRT/HDAC3 complex to exclude RNA Polymerase II and silence transcription, and remodel the 3-dimensional structure of the X chromosome to enable chromosome-wide RNA spreading and silencing.
One of these, RNA antisense purification (RAP), was developed by Jesse Engreitz, a former graduate student in his lab, along with Guttman.
Building on this, Guttman's team revisited the function of nuclear speckles, regions enriched in splicing factors, traditionally thought to be storage sites.
[7] This process helps cells produce the correct amounts of proteins required for proper cellular function.