MICRO RNA 4435-2 HOST GENE, NONCODING; MIR4435-2HG

Alternative titles; symbols

• MIR4435-2 HOST GENE
• miRNA4435-2 HOST GENE
• LONG NONCODING RNA MORRBID
• lncRNA MORRBID
• MYELOID RNA REGULATOR OF BIM-INDUCED DEATH

HGNC Approved Gene Symbol: MIR4435-2HG

Cytogenetic location: 2q13 Genomic coordinates (GRCh38): 2:111,195,865-111,495,160 (from NCBI)

▼ Description
MORRBID is a long noncoding RNA (lncRNA) that controls the survival of short-lived myeloid cells, including neutrophils, eosinophils, and classical monocytes, by suppressing the proapoptotic gene BIM (BCL2L11; 603827) (Kotzin et al., 2016).

▼ Cloning and Expression
By analyzing RNA sequencing data for mouse lncRNAs preferentially expressed in short-lived myeloid cells, Kotzin et al. (2016) identified Gm14005, which they termed Morrbid. MORRBID is conserved conserved across species, including human, and is polyadenylated. Morrbid localized predominantly to nucleus and was bound to chromatin in mouse bone marrow-derived macrophages. Quantitative PCR showed that MORRBID was highly and specifically expressed by mature eosinophils, neutrophils, and classical monocytes in mouse and human.

▼ Gene Structure
Kotzin et al. (2016) determined that the MORRBID gene contains 5 exons.

▼ Mapping
Kotzin et al. (2016) reported that the MORRBID gene is located downstream of the BIM gene in a tail-to-tail orientation in both mouse and human. The BIM gene maps to human chromosome 2q13 (Gross, 2016).

▼ Gene Function
Kotzin et al. (2016) found that knockdown of Morrbid in cultured mouse eosinophils or lipopolysaccharide-stimulated mouse macrophages via short hairpin RNA resulted in significant elevation of Bim. Treatment of cells with cytokines that promote survival of short-lived myeloid cells, such as Il3 (147740), Il5 (147850), or Gmcsf (CSF2; 138960), induced Morrbid expression and decreased Bim expression. Chromatin immunoprecipitation analysis showed that Morrbid, in conjunction with polycomb complex-2 members, such as Ezh2 (601573), repressed Bim expression in short-lived myeloid cells by promoting deposition of the repressive histone mark H3K27me3 (see 602810) at the bivalent promoter of Bim. Patients with hypereosinophilic syndrome (HES; 607685) expressed higher levels of MORRBID than controls, and this MORRBID overexpression correlated positively with IL5 plasma levels. Kotzin et al. (2016) concluded that MORRBID integrates extracellular signals to control the lifespan of eosinophils, neutrophils, and classical monocytes through allele-specific suppression of BIM expression.

▼ Animal Model
Kotzin et al. (2016) found that Morrbid -/- mice had reduced numbers of blood and tissue eosinophils, neutrophils, and classical monocytes, but not other lymphoid or myeloid cells or progenitors of these cell types. Morrbid -/- mice were highly susceptible to Listeria monocytogenes infection, but they were protected from eosinophil-driven allergic lung inflammation. Morrbid -/- eosinophils, neutrophils, and monocytes displayed increased apoptosis in vitro and in vivo during L. monocytogenes infection. Morrbid -/- cells showed elevated expression of Bim.