Anjelica Huston is on board to direct CBS’ upcoming “Riding the Bus With My Sister,” and Andie MacDowell will star opposite Rosie O’Donnell in the telepic.

MacDowell joins the cast as Rachel, a New York photographer who ends up spending more time with her mentally challenged sister Beth (O’Donnell) after their father dies. Estranged from her sister, Rachel begins riding with her on the bus — and discovers that Beth has created a whole new family via the drivers and passengers.

The actress’s recent feature credits include “Crush,” “Town and Country” and “The Muse.”

She also did a recent guest stint on “The Practice” and starred in the HBO telepic “Dinner With Friends.” MacDowell will next be seen in the Queen Latifah feature “Beauty Shop.”

Huston’s directing credits include “Agnes Browne” and “Bastard Out of Carolina.”

As an actress, Huston most recently appeared in the HBO telepic “Iron Jawed Angels,” as well as features “The Royal Tenenbaums” and “Daddy Day Care.” She’ll next be seen in “The Life Aquatic.”

Larry Sanitsky and O’Donnell exec produce “Riding the Bus With My Sister” for the Sanitsky Co.

(Josef Adalian contributed to this report.)