Visualization and modeling of the shape and motion of HOTAIR by AFM. (A) Field imaged at lower magnification showing free HOTAIR molecules, squares mark objects reliably assigned as properly folded HOTAIR. Large mass in the center of the field is an aggregate of dsDNA and HOTAIR RNA (bar = 500 nm). (B) Representative higher magnification images of HOTAIR molecules showing their distinct anatomy (bar = 50 nm). (C) Representative cryo-EM images of HOTAIR (bar = 50 nm). (D) Proposed molecular model of HOTAIR, divided into nine structural segments: (UL) U long, (US) U short, (N) neck, (HS) hand short, (HL) hand long, (T) torso, (P) pelvis, (LS) leg short, (LL) leg long. (E) Structural flexibility of HOTAIR expressed as variation in segment lengths. (F) The human figures frozen in various configurations are analogous to the concept of HOTAIR as a molecule with a distinct anatomy but also high flexibility.